1.Effect of Modified Tuoli Xiaodusan on Patients After Perianal Abscess Surgery on STAT3/VEGF Pathway
Haoyang DU ; Yuan GAO ; Haiqi FU ; Jinling HE ; Jing ZHANG ; Yangyang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):187-195
ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess, and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 (STAT3)/vascular endothelial growth factor (VEGF) signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine, 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method, with 30 cases in each group. The control group received conventional treatment, while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7th, 14th and 21st day after operation, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Hematoxylin eosin (HE) staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 (p-STAT3) and vascular endothelial growth factor (VEGF) proteins, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain, secretion volume score, and healing rate of patients on the 3rd, 7th, 14th, and 21st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group (P<0.05). For intra-group comparison, the pain score of the control group decreased at each time period (P<0.05), and the healing rate increased (P<0.05). The secretion volume score decreased on the 14th and 21st days after operation (P<0.05). The pain score and secretion volume score of the treatment group decreased at each time period (P<0.05), and the healing rate increased (P<0.05). The levels of various inflammatory factors decreased in both groups (P<0.05). Compared with those on the surgical day, the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7th and 21st days after operation (P<0.05). There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period (P<0.01). For inter-group comparison, on the 7th and 14th days after operation, the pain score in the treatment group was lower than that in the control group. On the 7th, 14th and 21st days after operation, the secretion volume scores and healing rate of the treatment group were better than those of the control group (P<0.05). The levels of various inflammatory factors in the treatment group were lower than those in the control group (P<0.05), and the decline rate was faster (P<0.05). On the 7th day after operation, the levels of p-STAT3, VEGF protein, and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group (P<0.05). HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly, and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery, reduce secretions, and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β, IL-6, and TNF-α, reducing the inflammatory response of the wound, upregulating the expression of p-STAT3 and VEGF proteins, and stimulating the STAT3/VEGF signaling pathway, thereby accelerating angiogenesis and promoting wound healing.
2.Effect of Yiqi Wenyang Huoxue Lishui Components on Cardiac Function and Mitochondrial Energy Metabolism in CHF Rats
Hui GAO ; Zeqi YANG ; Xin LIU ; Fan GAO ; Yangyang HAN ; Aiyangzi LU ; Xingchao LIU ; Qiuhong GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):27-36
ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure (CHF) and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction (TAC). Eight of the 50 SD rats were randomly selected as the sham group, and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model, trimetazidine (6.3 mg·kg-1), and Yiqi Wenyang Huoxue Lishui components (60 mg·kg-1 total saponins of Astragali Radix, 10 mg·kg-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma, 190 mg·kg-1 aqueous extract of Lepidii Semen, and 100 mg·kg-1 cinnamaldehyde) groups. The rats were administrated with corresponding agents by gavage, and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide (NT-ProBNP), hypersensitive troponin(cTnI), creatine kinase (CK), lactate dehydrogenase (LD), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA). The colorimetric assay was employed to measure the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta (ATP5D), glucose transporter 4 (GLUT4), and carnitine palmitoyltransferase-1 (CPT-1). The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ, Ⅱ, Ⅲ, and Ⅳ. ResultsCompared with the sham group, the model group showed a loosening arrangement of cardiac fibers, fracture and necrosis of partial cardiac fibers, inflammatory cells in necrotic areas, massive blue fibrotic tissue in the myocardial interstitium, increased collagen fiber area and myocardial fibrosis, destroyed mitochondria, myofibril disarrangement, sparse myofilaments, and fractured and reduced cristae. In addition, the rats in the model group showed declined ejection fraction (EF) and fractional shortening (FS), risen left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular end-systolic posterior wall thickness (LVPWs), left ventricular end-diastolic volume (LVVOLd), and left ventricular end-systolic volume (LVVOLs), elevated levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, lowered level of SOD, down-regulated protein levels of GLUT4 and CPT-1, decreased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and declined levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). Compared with the model group, the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue, risen EF and FS, declined LVIDd, LVIDs, LVPWd, LVPWs, LVVOLd, and LVVOLs, lowered levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, elevated level of SOD, up-regulated protein levels of GLUT4 and CPT-1, increased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and elevated levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function, reduce myocardial injury, regulate glucose and lipid metabolism, optimize the utilization of substrates, and alleviate the damage of mitochondrial structure and function, thus improving the energy metabolism of the myocardium in the rat model of CHF.
3.Research progress on Astragali Radix for promoting healing of chronic refractory wound
Yangyang YU ; Yuan GAO ; Jinling HE ; Hao WU ; Keyu CHEN ; Yuxing ZHAO
China Pharmacy 2025;36(19):2473-2478
Chronic refractory wound (CRW) presents significant clinical treatment challenges due to pathological characteristics such as persistent inflammation, bacterial infection, oxidative stress and inadequate angiogenesis. Astragali Radix, a traditional Chinese medicinal herb, exerts multi-target pharmacological effects on CRW through its active components, including Astragalus polysaccharides, flavonoids, and astragaloside Ⅳ, etc. Fundamental studies indicate that these components promote CRW healing by modulating inflammatory responses, inhibiting pathogen growth, improving antioxidant capacity and stimulating neovascularization. Network pharmacology and bioinformatics studies have revealed that active components of Astragali Radix target and modulate key signaling nodes such as nuclear factor-κB, phosphatidylinositol 3-kinase/Akt, AMP-activated protein kinase, and vascular endothelial growth factor receptor, as well as inflammation-angiogenesis-related pathways, thereby synergistically exerting anti-inflammatory and pro-angiogenic effect. Clinical applications have demonstrated that oral formulations (e.g., Huangqi guizhi decoction, Danggui huangqi decoction, etc.) reduce healing time of CRW and lower inflammatory marker levels, while topical preparations (e.g., Zizhu ointment, Huangqi shengji ointment, electrostatically spun Astragalus polysaccharide composite nanofibre dressings, etc.) significantly improve healing rates of CRW and minimize complications.
4.Therapeutic effect of Rhizoma Corydalis on ulcerative colitis induced by dextran sodium sulfate and its mechanism:a study based on metabolomics
Chentao XIE ; Jialing LIU ; Yangyang GAO ; Haoran XU ; Hui WANG ; Yuanjing ZHAO ; Ruyi FAN ; Simin CHEN
Journal of Chongqing Medical University 2025;50(7):879-888
Objective:To investigate the interventional effect of Rhizoma Corydalis on mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),as well as the potential mechanism of Rhizoma Corydalis in the treatment of UC based on metabolomics and inflammation biomarkers.Methods:A mouse model of UC was established,and then the mice were divided into model group,high-dose group(1.517 g/kg crude drug),middle-dose group(0.986 g/kg crude drug),low-dose group(0.455 g/kg crude drug),and positive drug group(5-aminosalicylic acid at a dose of 718.8 mg/kg),while the mice without modeling were selected as normal group(0.9%NaCl by gavage).The mice in each group were administered for 7 consecutive days,and phenotypic parameters were dynamically moni-tored,such as body weight change,disease activity index(DAI),mean daily food intake,and daily water intake.The mice were sacri-ficed after 7 days to collect serum and colon tissue samples;ELISA was used to measure the serum levels of the proinflammatory fac-tors interleukin-6(IL-6),interleukin-17A(IL-17A),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α),and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was used to perform the non-targeted metabolomics analysis and compare the differences in se-rum metabolite profiles between groups.The mice were selected for modeling and validation with the same method,and glutathione(GSH)was selected as the positive drug.Colon length and mucosal damage were assessed,and quantitative real-time PCR was used to measure the relative mRNA expression levels of the key genes in the glutathione synthesis pathway(γ-glutamylcysteine synthetase[γ-GCS]and oxidative stress regulators yap1p and skn7)and mito-chondrial GSH transporter protein(Slc25a39)in colonic tissue.Results:Rhizoma Corydalis significantly improved weight loss,DAI,and colon length in a dose-dependent manner in the model animals,and there were reductions in the serum levels of IL-6,CRP,and TNF-α,while it had no significant effect on IL-17A.The metabolomics analysis revealed 21 potential biomarkers associated with amino acid and lipid metabolism,which were significantly regulated by Rhizoma Corydalis.In the verification experiment,both Rhi-zoma Corydalis and GSH exerted a significant protective effect against colonic mucosal damage without affecting colon length.Rhizoma Corydalis upregulated the expression of genes associated with glutathione synthesis,especially γ-GCS,suggesting that Rhizoma Co-rydalis could enhance intestinal antioxidant defenses.Conclusion:Rhizoma Corydalis has a therapeutic potential in a mouse model of DSS-induced UC and can alleviate symptoms,reduce the serum levels of inflammatory markers,and regulate metabolic pathways,and upregulation of the genes associated with glutathione synthesis suggests that the drug can enhance intestinal antioxidant defenses.
5.Clinical effects of free superficial circumflex iliac artery superficial branch perforator flap combined with full-thickness skin graft far from the flap donor site in repairing the large wounds in extremities
Yangyang LIU ; Min WU ; Jun ZHU ; Kuankuan ZHANG ; Haizhou NIU ; Xubin GAO ; Zhongbing HAN ; Fendou LIU
Chinese Journal of Burns 2024;40(1):72-77
Objective:To investigate the clinical effects of free superficial circumflex iliac artery (SCIA) superficial branch perforator flap combined with full-thickness skin graft far from the flap donor site in repairing the large wounds in extremities.Methods:The study was a retrospective observational study. From January 2020 to June 2022, 19 patients with large wounds in extremities who met the inclusion criteria were admitted to the First Affiliated Hospital of Bengbu Medical College, including 15 males and 4 females, aged 28-75 years. The debridement, fracture reduction and fixation, tendon, vessel, and nerve repair, and vacuum sealing drainage were performed in the first stage surgery. After debridement in the second stage surgery, the total wound area was 13.0 cm×8.0 cm-34.0 cm×15.0 cm. The tendon and bone exposed wound with area of 9.0 cm×6.0 cm-14.0 cm×7.0 cm was repaired with free SCIA superficial branch perforator flap with area of 10.0 cm×6.5 cm-15.0 cm×8.0 cm. The remaining granulation tissue wound with area of 5.0 cm×3.5 cm-13.0 cm×8.0 cm was repaired with full-thickness skin graft far from the flap donor site with area of 5.0 cm×3.5 cm-13.0 cm×8.0 cm. All the wounds in donor site were sutured. The operation time and amount of bleeding of patients during the surgery were recorded, the survival of flap and skin graft were observed after surgery. During follow-up, the flap and skin graft, scar in the donor site and its effect on donor site function were observed. At the last follow-up, the satisfaction of patients with the efficacy was evaluated by the efficacy satisfaction rating score.Results:The operation time of patients was 2.0-3.5 h. The amount of bleeding of patients during the surgery was 100-320 mL. One patient had ecchymosis and venous crisis in the edge of flap on the second day after surgery, and the flap survived after exploration. The flaps of the other patients survived smoothly. The skin grafts of patients all survived smoothly. Two patients had bloated flaps due to obesity in the later stage, and the expected results were achieved after flap thinning surgery 6 months after operation. During the follow-up of 6 to 24 months, the flaps had good elasticity and soft texture, and the skin grafts had no wear or ulceration; linear scars were left in all the donor sites but their functions were not affected. The patients were all satisfied with the efficacy.Conclusions:Free SCIA superficial perforator flap combined with full-thickness skin graft far from the donor site was used to repair the large wounds in extremities, which was safe, reliable, and less traumatic and short in operation time, and resulted in good postoperative appearance and function in the donor sites and recipient sites.
6.Exploring optimal tamoxifen labeling dose in myocardial cell prolifera-tion using Brainbow tracing mice
Yangyang GAO ; Jia GAO ; Meng SUN ; Rui WANG
Chinese Journal of Pathophysiology 2024;40(6):1147-1152
AIM:This study employs Brainbow 2.1 mice to trace myocardial cell lineage and investigates the optimal dose of tamoxifen for labeling proliferating myocardial cells.METHODS:Four-week-old Brainbowfl/+;Myh6-Mer-CreMer+mice were administered tamoxifen at three different doses(3,9 and 27 mg/kg)via intraperitoneal injection to in-duce Cre recombinase expression and label myocardial cells with specific colors.Four weeks later,the samples were stained,and the number of myocardial cells labeled with varying doses of tamoxifen was quantified under confocal micro-scope.This quantification included the proportion of individually labeled cells,adjacent clusters of two cells,and clusters of three or more cells.An appropriate dose(9 mg/kg)of tamoxifen for labeling Brainbow mice was selected to compare myocardial cell proliferation between sham and myocardial infarction(MI)model groups.RESULTS:(1)After 9 mg/kg tamoxifen injection,the proportion of individually labeled cells was 99.13%±0.03%,that of adjacent 2-cell clusters was 0.82%±0.09%,and that of≥3-cell clusters was 0.05%±0.01%.The 3 mg/kg group had fewer total labeled cells,while the 27 mg/kg group showed significant clonal expansion and enrichment.(2)After labeling myocardial cells with 9 mg/kg tamoxifen,the MI mice showed increased proportions of 2-cell and≥3-cell clusters compared with sham group(P<0.01),indicating an increase in myocardial cell proliferation after MI.CONCLUSION:The proportion of adjacent myocardial cell clusters labeled with 9 mg/kg tamoxifen more closely approximates the physiological myocardial cell proliferation rate,indicating 9 mg/kg as the most suitable tamoxifen dose for tracing myocardial cell proliferation.
7.Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia
Ning WANG ; Yangyang GAO ; Benquan QI ; Min RUAN ; Hui LYU ; Xiaoyan ZHANG ; Ranran ZHANG ; Tianfeng LIU ; Yumei CHEN ; Yao ZOU ; Ye GUO ; Wenyu YANG ; Li ZHANG ; Xiaofan ZHU ; Xiaojuan CHEN
Chinese Journal of Pediatrics 2024;62(3):262-267
Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.
8.The application of kissing-stent in treating chronic iliac-vena cava occlusion
Shaobo ZHAI ; Zhixiang LV ; Zhihua ZHANG ; Jifeng SUN ; Yangyang YU ; Cheng GAO
Journal of Interventional Radiology 2024;33(7):763-766
Objective To evaluate the clinical efficacy of kissing-stent implantation in the treatment of chronic iliac-vena cava occlusion.Methods The clinical data of 22 patients with chronic iliac-vena cava occlusion,who received kissing-stent implantation,were retrospectively analyzed.The surgical success rate and the procedure-related complications were recorded,the postoperative 3-,6-and 12-month stent patency rates were calculated,and the postoperative 6-month Villalta score was compared with its preoperative value.Results The technical success rate of kissing-stent implantation was 100%.No procedure-related surgical complications occurred.The postoperative 3-,6-and 12-month stent patency rates were 95.5%,90.9%and 86.1%respectively.The postoperative 6-month Villalta score was(12.14±2.80)points,which was remarkably lower than preoperative(20.91±3.16)points,the difference was statistically significant(P<0.05).Conclusion The implantation of kissing-stent can successfully reconstruct iliac-vena cava with satisfactory short-term efficacy for chronic iliac-vena cava occlusion.
9.Treatment of Asthenospermia and Infertility with Liver Constraint and Kidney Deficiency in 45 Cases by Shugan Bushen Yulin Decoction (疏肝补肾毓麟汤) and Vitamin E Soft Capsules: A Multicenter Randomized Controlled Trial
Wang WANG ; Jigang CAO ; Min XIAO ; Yangyang ZHU ; Mengjie GAO ; Qikai WANG ; Xiaocui JIANG ; Heng HAO ; Siyi CHEN
Journal of Traditional Chinese Medicine 2024;65(18):1909-1914
ObjectiveTo observe the clinical efficacy and safety of Shugan Bushen Yulin Decoction (疏肝补肾毓麟汤, SBYD) in the treatment of asthenospermia and infertility with liver constraint and kidney deficiency. MethodsA multicenter, randomized, controlled clinical study was conducted in three hospitals in central China. Totally 95 patients with asthenospermia and infertility were controlled. According to random number table, the patients were divided into treatment group (47 cases) and control group (48 cases). The control group was given vitamin E soft capsules (100 mg per time, twice daily) orally, and the treatment group was given SBYD (one dose daily, 30 min after breakfast and dinner, about 200 ml each time) orally. The course of treatment was 12 weeks in both groups. After the treatment, the sperm concentration, percentage of forward motile sperm (PR), and percentage of total sperm activity, that is PR + percentage of non-progressively motile sperm (NP) were compared between groups, and the clinical efficacy was judged. Traditional Chinese medicine (TCM) syndrome score (inlcuding 6 single symptom scores and total symptoms score) and 21-item depression, anxiety, and stress scale (DASS-21) scores (including depression, anxiety and stress scores) were compared between the two groups before and after treatment. The patients were followed up for 6 months, and the pregnancy status of spouse between groups was compared. The occurrence of adverse events and vital signs during the trial were recorded for safety assessment. ResultsTwo cases in the treatment group and three cases in the control group dropped out. Finally, 45 cases in each group were included in the statistical analysis. The total effective rate was 86.67% (39/45) in the treatment group, significantly higher than 73.74% (33/45) in the control group (P<0.05). After treatment, PR and PR + NP significantly increased in both groups, and were much higher in the treatment group than in the control group (P<0.05). The scores of lumbar and knee soreness, emotional disturbance, cold sperm, chest and rib-side and lesser abdomen distension and pain, frequent sighing, and the total TCM syndrome score in the treatment group decreased after treatment (P<0.05); and except for cold sperm, the scores of other symptoms mentioned above as well as the total TCM syndrome score in the treatment group were lower than those in the control group (P<0.05). The scores of depression, anxiety and stress of DASS-21 in the treatment group decreased after treatment, and were lower than those in the control group (P<0.05). After 6 months of follow-up, the spouses of 5 patients in the treatment group and 3 patients in the control group got pregnant (P>0.05). No adverse events occurred in both groups during the treatment, and their vital signs were stable. ConclusionSBYD can obviously improve sperm vitality and effectively improve the clinical symptoms, anxiety and depression, and is safe in treating asthenospermia and infertility with liver constraint and kidney deficiency.
10.Effect of sorafenib induced apoptosis and autophagy on drug resistance in HeLa cells
Kaifei YANG ; Jingge ZHU ; Yangyang ZHANG ; Junguo ZHAO ; Yuyue GAO ; Huanhuan HU ; Guojie JI
Basic & Clinical Medicine 2024;44(4):467-473
Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P<0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P<0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

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