1.Mechanism of Modified Si Junzitang and Shashen Maidong Tang in Improving Sensitivity of Cisplatin in EGFR-TKI Resistant Lung Adenocarcinoma Cells Based on Aerobic Glycolysis
Yanping WEN ; Yi JIANG ; Liping SHEN ; Haiwei XIAO ; Xiaofeng YANG ; Surui YUAN ; Lingshuang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):39-46
ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang [Yiqi Yangyin Jiedu prescription (YQYYJD)] in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD (0, 2, 3, 4, 5, 6, 7, 8 g·L-1) and cisplatin (0, 3, 6, 9, 12, 15, 18, 21, 24, 27 mg·L-1) on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 (CCK-8) assay after 24 hours of intervention. The half-maximal inhibitory concentration (IC50) for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group (complete medium), YQYYJD group (5 g·L-1), cisplatin group (12 mg·L-1), and combined group (YQYYJD 5 g·L-1 + cisplatin 12 mg·L-1). After 24 hours of intervention, cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay, and cell migration was evaluated by scratch and Transwell assays. Glucose consumption, lactate production, and adenosine triphosphate (ATP) levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins, including hexokinase 2 (HK2), phosphofructokinase P (PFKP), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1), and monocarboxylate transporter 4 (MCT4), were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC50 of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L-1 and 12.91 mg·L-1, respectively. In terms of cell proliferation, compared with the blank group, the cell survival rate and the number of colonies formed in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in cell survival rate and colony formation (P<0.01). In terms of cell migration, compared with the blank group, the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane (P<0.01). In terms of glycolysis, compared with the blank group, glucose consumption, lactate production, and ATP levels in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in glucose consumption, lactate production, and ATP levels (P<0.05). Compared with the blank group, the protein expression levels of HK2, PFKP, PKM2, and LDHA in the YQYYJD, cisplatin, and combined groups were significantly decreased (P<0.01). The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups (P<0.01). No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes, including HK2, PFKP, PKM2, and LDHA, thereby inhibiting glycolysis.
2.Expert consensus on dispensing management of intravenous infusion drugs for clinical trials in PIVAS
Xingchen YANG ; Wenhuan FU ; Donghui LAO ; Jing ZHAO ; Jianzhong ZHANG ; Group PHARMACY ; Committee HOSPITAL ; Association Pharmaceutical SHANGHAI
China Pharmacy 2025;36(1):1-6
OBJECTIVE To further standardize the dispensing management standard of intravenous infusion drugs for clinical trials in pharmacy intravenous admixture services (PIVAS), and provide reference for medical institutions to provide high-quality pharmaceutical services. METHODS Initiated by PIVAS Group, Hospital Pharmacy Professional Committee, Shanghai Pharmaceutical Association, jointly led by Longhua Hospital, Shanghai University of Traditional Chinese Medicine and Shanghai Geriatric Medical Center, a writing group was established by PIVAS experts from multiple medical institutions to discuss the basic requirements and dispensing process of intravenous infusion drugs for clinical trials in PIVAS. The experts from the leading unit sorted out, summarized, analyzed, fed back and revised the opinions, and finally reached Expert Consensus on Dispensing Management of Intravenous Infusion Drugs for Clinical Trials in PIVAS. RESULTS & CONCLUSIONS The main contents of this consensus include information management, operation process, fund management and document management of intravenous infusion drugs for clinical trials in PIVAS. This consensus establishes a more standardized model for dispensing management of intravenous infusion drugs for clinical trials in PIVAS, by standardizing clinical trail drug management operational procedures, accurately recording and preserving drug-related information, with the aim of achieving standardized and meticulous management of PIVAS’s receipt of clinical trial drugs.
3.Weichang'an Prescription-containing Serum Induces Ferroptosis of Gastric Cancer MKN-45 Cells
Xin LI ; Jinzu YANG ; Jianxin QIAN ; Li TAO ; Ling CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):132-139
ObjectiveTo observe the effect of Weichang'an prescription-containing serum on ferroptosis of human gastric cancer cells and explore the possible mechanism. MethodsSD rats were administrated with 18, 36, 72 g·kg-1·d-1 Weichang'an prescription by gavage for preparation of serum samples containing different doses of Weichang'an prescription, which were then used to treat MKN-45 cells. The cell proliferation was examined by the cell counting kit-8 (CCK-8). In addition, inhibitors of apoptosis, necroptosis, and ferroptosis were added, and the survival of the cells treated with the serum samples was observed. The fluorescent probe dichlorodihydrofluorescein diacetate (DCF-DA) and the lipid peroxidation sensor C11-BODIPY were employed to detect the intracellular levels of reactive oxygen species (ROS) and lipid peroxidation, respectively. The levels of ferrous ion (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blotting were employed to determine the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), aldo-keto reductase family 1 member B1 (AKR1B1), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK). ResultsCompared with the blank group, Weichang'an prescription-containing serum decreased the viability of MKN-45 cells (P<0.05, P<0.01) in a time- and dose-dependent manner. Compared with the Weichang'an prescription group, the apoptosis inhibitor+Weichang'an prescription group and the ferroptosis inhibitor+Weichang'an prescription group showed increased cell viability (P<0.05, P<0.01). Compared with the blank group, Weichang'an prescription elevated the levels of ROS, lipid peroxidation, and intracellular Fe2+ and MDA (P<0.05, P<0.01) and lowered the level of GSH (P<0.05, P<0.01) in a dose-dependent manner. Compared with the blank group, Weichang'an prescription down-regulated the mRNA and protein levels of Nrf2, AKR1B1, and GPX4 (P<0.05, P<0.01) and up-regulated the mRNA and protein levels of ACSL4 (P<0.05, P<0.01) in a dose-dependent manner. Compared with the blank group, Weichang'an prescription down-regulated the protein levels of p-STAT3 and p-ERK (P<0.05, P<0.01) in a dose-dependent manner. ConclusionThe Weichang'an prescription-containing serum can promote the ferroptosis and inhibit the proliferation of MKN-45 cells by regulating the STAT3 and MAPK pathways.
4.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
5.Translational Research of Electromagnetic Fields on Diseases Related With Bone Remodeling: Review and Prospects
Peng SHANG ; Jun-Yu LIU ; Sheng-Hang WANG ; Jian-Cheng YANG ; Zhe-Yuan ZHANG ; An-Lin LI ; Hao ZHANG ; Yu-Hong ZENG
Progress in Biochemistry and Biophysics 2025;52(2):439-455
Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.
6.Oxidative Stress of Qidan Tangshen Granules (芪丹糖肾颗粒) in Treatment of 95 Patients with Early Diabetic Kidney Disease with Qi Deficiency,Blood Stasis,and Kidney Deficiency Syndrome:A Double-Blind,Double-Simulated,Randomized Controlled Trial
Jie ZHANG ; Yilei CONG ; Tengfei WU ; Qin LIU ; Yue YUAN ; Shilei CUI ; Hua YANG
Journal of Traditional Chinese Medicine 2025;66(7):695-703
ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules (芪丹糖肾颗粒, QTG) in the treatment of early diabetic kidney disease (DKD) with qi deficiency, blood stasis, and kidney deficiency syndrome, and to explore its mechanism. MethodsA double-blind, double-simulated method was used to enroll 200 patients with early DKD and qi deficiency, blood stasis, and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group (100 cases) and the control group (100 cases). The treatment group received QTG plus a valsartan capsule simulant, while the control group received valsartan capsules plus a QTG simulant, both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio (UACR). Secondary outcomes included estimated glomerular filtration rate (eGFR), fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG), glycated hemoglobin (HbA1c), and traditional Chinese medicine (TCM) syndrome scores (including individual symptom scores for fatigue, dull complexion, soreness and weakness of the waist and knees, headache and chest pain, irritability, spontaneous sweating, thirst and polydipsia, polyphagia, polyuria, numbness of the limbs, and the total TCM syndrome score). Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine (8-OHDG), 3-nitrotyrosine (3-NT), and superoxide dismutase (SOD) were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment, and routine blood tests, urinalysis, and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study (95 in the treatment group and 96 in the control group). The treatment group showed significant reductions in UACR, FBG, PBG, and HbA1c levels after treatment (P<0.05 or P<0.01). The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased (P<0.05 or P<0.01). Compared to the control group, the treatment group had signi-ficantly lower UACR, FBG, PBG levels, and total TCM syndrome scores, sinlge symptoms scores except for polyphagia and limb numbness (P<0.05 or P<0.01). Among 40 randomly selected patients (21 cases in the treatment group and 19 cases in the control group) for oxidative stress analysis, there were no significant differences in SOD, 3-NT, and 8-OHDG levels before and after treatment within or between groups (P>0.05). The overall effective rate in the treatment group was 64.2% (61/95) and 39.6% (38/96) in the control group, while the TCM syndrome efficacy rates were 80.0% (76/95) and 24.0% (23/96), respectively, with the treatment group showing superior efficacy (P<0.01). No significant differences were observed in routine blood tests, urinalysis, or liver function indices before and after treatment in either group (P>0.05). The incidence of adverse reactions was 8.4% (8/95) in the treatment group and 9.4% (9/96) in the control group, with no statistically significant difference (P>0.05). ConclusionQTG can effectively reduce UACR and blood glucose levels, alleviate clinical symptoms, and improve clinical efficacy in patients with early DKD with qi deficiency, blood stasis, and kidney deficiency syndrome. The treatment is well-tolerated and safe, with no significant impact on oxidative stress markers.
7.Trends in global burden due to visceral leishmaniasis from 1990 to 2021 and projections up to 2035
Guobing YANG ; Aiwei HE ; Yongjun LI ; Shan LÜ ; Muxin CHEN ; Liguang TIAN ; Qin LIU ; Lei DUAN ; Yan LU ; Jian YANG ; Shizhu LI ; Xiaonong ZHOU ; Jichun WANG ; Shunxian ZHANG
Chinese Journal of Schistosomiasis Control 2025;37(1):35-43
Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/105, 95% UI: (1.49/105, 4.07/105)], prevalence [0.64/105, 95% UI: (0.37/105, 1.02/105)], mortality [0.51/105, 95% UI: (0, 1.80/105)] and DALYs rates of VL [33.81/105, 95% UI: (0.06/105, 124.09/105)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/105, 95% UI: (0.45/105, 0.72/105); 0.14/105, 95% UI: (0.11/105, 0.18/105)] than among women [0.27/105, 95% UI: (0.21/105, 0.33/105); 0.06/105, 95% UI: (0.05/105, 0.08/105)], and the highest mortality of VL was found among children under 5 years of age [0.24/105, 95% UI: (0.08/105, 0.66/105)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/105, 0.03/105, 0.02/105 and 1.44/105 in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.
8.Feiyanning Inhibits Invasion and Metastasis of Non-small Cell Lung Cancer by Regulating EMT via TGF-β1/Smad Signaling Pathway
Xiaojie FU ; Jia YANG ; Kaile LIU ; Wenjie WANG ; Zhenye XU ; Zhongqi WANG ; Haibin DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):110-120
ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition (EMT) and invasion and metastasis of non-small cell lung cancer (NSCLC). MethodsCell proliferation and activity were assessed using the cell counting kit-8(CCK-8) assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β1 was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β1-induced NSCLC cell metastasis, EMT, and the TGF-β1/Smad pathway proteins were assessed by wound healing assay, Transwell assay, and Western blot. In vivo, an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups: Model (NC) group, Feiyanning low-dose (FYN1) group, Feiyanning high-dose (FYN2) group, and the positive control group (TGF-β receptor kinase inhibitor SB431542 group). The corresponding interventions were performed. After 40 days, the mice were euthanized, and lung metastases were analyzed. The expression of E-cadherin, N-cadherin, p-Smad2, and p-Smad3 in each group was detected by immunohistochemistry (IHC). ResultsAfter Feiyanning intervention, compared to the blank group, Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner (P<0.01). The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group (P<0.01). The expression of EMT marker proteins N-cadherin and zinc finger transcription factors (Zeb1, Snail, Slug) was significantly reduced in the Feiyanning groups compared to the blank group (P<0.05, P<0.01). The expression of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ, key proteins in the TGF-β1/Smad signaling pathway, was also significantly decreased (P<0.01). In the TGF-β1-induced EMT model, compared to the TGF-β1 group, the cell metastasis ability in the Feiyanning groups was reduced (P<0.01), and the expression levels of N-cadherin, Zeb1, Snail, and Slug were significantly lower (P<0.01). The expression levels of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ were also significantly reduced (P<0.01). In vivo results showed that compared to the model group, the number of lung metastases in the FYN1, FYN2, and SB431542 groups was reduced (P<0.01), and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group, the expression of E-cadherin in the FYN1, FYN2, and SB431542 groups was increased (P<0.01), the expression of N-cadherin decreased (P<0.05, P<0.01), and the expression of p-Smad2 and p-Smad3, key proteins of the TGF-β1/Smad pathway, was reduced (P<0.01). ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β1/Smad signaling pathway.
9.Feiyanning Inhibits Invasion and Metastasis of Non-small Cell Lung Cancer by Regulating EMT via TGF-β1/Smad Signaling Pathway
Xiaojie FU ; Jia YANG ; Kaile LIU ; Wenjie WANG ; Zhenye XU ; Zhongqi WANG ; Haibin DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):110-120
ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition (EMT) and invasion and metastasis of non-small cell lung cancer (NSCLC). MethodsCell proliferation and activity were assessed using the cell counting kit-8(CCK-8) assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β1 was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β1-induced NSCLC cell metastasis, EMT, and the TGF-β1/Smad pathway proteins were assessed by wound healing assay, Transwell assay, and Western blot. In vivo, an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups: Model (NC) group, Feiyanning low-dose (FYN1) group, Feiyanning high-dose (FYN2) group, and the positive control group (TGF-β receptor kinase inhibitor SB431542 group). The corresponding interventions were performed. After 40 days, the mice were euthanized, and lung metastases were analyzed. The expression of E-cadherin, N-cadherin, p-Smad2, and p-Smad3 in each group was detected by immunohistochemistry (IHC). ResultsAfter Feiyanning intervention, compared to the blank group, Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner (P<0.01). The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group (P<0.01). The expression of EMT marker proteins N-cadherin and zinc finger transcription factors (Zeb1, Snail, Slug) was significantly reduced in the Feiyanning groups compared to the blank group (P<0.05, P<0.01). The expression of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ, key proteins in the TGF-β1/Smad signaling pathway, was also significantly decreased (P<0.01). In the TGF-β1-induced EMT model, compared to the TGF-β1 group, the cell metastasis ability in the Feiyanning groups was reduced (P<0.01), and the expression levels of N-cadherin, Zeb1, Snail, and Slug were significantly lower (P<0.01). The expression levels of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ were also significantly reduced (P<0.01). In vivo results showed that compared to the model group, the number of lung metastases in the FYN1, FYN2, and SB431542 groups was reduced (P<0.01), and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group, the expression of E-cadherin in the FYN1, FYN2, and SB431542 groups was increased (P<0.01), the expression of N-cadherin decreased (P<0.05, P<0.01), and the expression of p-Smad2 and p-Smad3, key proteins of the TGF-β1/Smad pathway, was reduced (P<0.01). ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β1/Smad signaling pathway.
10.Research progress on active components of traditional Chinese medicine inhibiting esophageal carcinoma by targeting mitochondrial apoptosis pathway
Junke XIAO ; Xiaoyan MU ; Jiaojiao GUO ; Shangzhi YANG ; Xuewei CAO ; Zhizhong GUO
China Pharmacy 2025;36(10):1283-1288
Esophageal carcinoma is a malignant disease with a high incidence rate and poor prognosis. The mitochondrial apoptosis pathway plays a pivotal role in the regulation of cell death and has become a focal point in current cancer therapeutics research. Various active components from traditional Chinese medicine (TCM) can target the mitochondrial apoptosis pathway to inhibit esophageal carcinoma, presenting as potential therapeutic agents for this disease. This paper summarizes relevant research on the inhibition of esophageal carcinoma by active components in TCM via targeting the mitochondrial apoptosis pathway. It has been found that flavonoids (casticin, icariin, luteolin, kaempferol, hesperetin, deguelin, etc.), terpenoids (oridonin, Jaridonin, artesunate, ethyl acetate fraction of pleurotus ferulatus triterpenoid, etc.), alkaloids (matrine, swainsonine, etc.), polyphenols (curcumin, epigallocatechin-3-gallate, corilagin, etc.), steroids (α-hederin, polyphyllin Ⅵ, etc.), phenols (optimized scorpion venom peptide CT-K3K7, gecko active polypeptide, etc.), volatile oils (cinnamaldehyde, α -asarone, etc.) and other active components from TCM can target the intrinsic mitochondrial apoptosis pathway, induce apoptosis in esophageal carcinoma cells, and inhibit their proliferation, invasion and migration by regulating oxidative stress, blocking the cell cycle, regulating signaling pathways such as PI3K/Akt and MAPK.

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