1.Analysis of the relationship between Hp infection and the expression of p27,CyclinD1,MMP-9 proteins and the related microRNAs and clinicpathological features in gastric cancer
Jian ZHAO ; Min DAI ; Ran SUN ; Yajun XU
The Journal of Practical Medicine 2025;41(18):2890-2897
Objective To investigate the association between Helicobacter pylori(Hp)infection and the expression levels of p27,CyclinD1,matrix metalloproteinase 9(MMP-9),and related microRNAs,as well as their correlations with clinicopathological characteristics in gastric cancer(GC)tissues.Methods A total of 116 GC patients who underwent surgical resection were enrolled and classified into Hp-positive and Hp-negative groups based on Hp infection status,consisting of 76 and 40 cases,respectively.Among the Hp-positive group,patients were further categorized into good prognosis and poor prognosis subgroups according to their clinical outcomes,with 56 and 20 cases,respectively.The expression levels of p27,CyclinD1,MMP-9 proteins,as well as miR-490-3p and miR-146a in both cancerous and paracancerous tissues across the groups were compared.Additionally,the associations between the expression of these biomarkers in cancer tissues and the clinicopathological features and prognosis of Hp-positive GC patients were analyzed.Furthermore,potential risk factors contributing to poor progno-sis in Hp-positive GC patients were identified,and a predictive model was constructed to evaluate its prognostic value.Results The expression levels of p27 protein and miR-490-3p in GC tissues were significantly lower compared to those in adjacent non-cancerous tissues,whereas the expression levels of CyclinD1,MMP-9 protein,and miR-146a were significantly higher(P<0.05).In cancer tissues from the Helicobacter pylori(Hp)-positive group,the expression of p27 protein and miR-490-3p was lower than that in the Hp-negative group,while the expression of CyclinD1,MMP-9 protein,and miR-146a was higher(P<0.05).Moreover,in Hp-positive GC patients,the expression levels of p27 protein and miR-490-3p in cancer tissues were lower in those with advanced stages(Ⅲ~Ⅳ)and lymph node metastasis compared to those with early stages(Ⅰ~Ⅱ)and no lymph node metastasis(P<0.05).Conversely,the expression levels of CyclinD1,MMP-9 protein,and miR-146a were higher in patients with advanced stages and lymph node metastasis(P<0.05).Compared with the good prognosis group,the poor progno-sis group exhibited a higher proportion of advanced stages,lymph node metastasis,and elevated expression levels of CyclinD1,MMP-9 protein,and miR-146a,while the expression levels of p27 protein and miR-490-3p were reduced(P<0.05).Multivariate analysis indicated that advanced stage(Ⅲ~Ⅳ),low expression of p27 pro-tein,high expression of MMP-9 protein,and low expression of miR-490-3p were independent risk factors for poor prognosis in Hp-positive GC patients(P<0.05).The predictive model constructed for assessing the likelihood of poor prognosis in Hp-positive GC demonstrated an area under the curve(AUC)of 0.774,with a sensitivity of 80.00%and a specificity of 76.79%.Conclusions p27,CyclinD1,MMP-9 protein,miR-146a,and miR-490-3p were found to be abnormally expressed in patients with Hp-positive GC.Their expression levels were significantly associated with TNM stage and the presence of lymph node metastasis.Specifically,Stage Ⅲ~Ⅳ disease,low expression of p27 protein and miR-490-3p,and high expression of MMP-9 protein were identified as independent risk factors for poor prognosis in patients with Hp-positive GC.A predictive model based on these risk factors demonstrated favorable performance in forecasting poor clinical outcomes in this patient population.
2.Effects of Bushen Tongfu Prescription on gut microbiota and LPS/TLR4/NF-κB pathway in APP/PS1 mice based on"microorganism-intestine-brain axis"
Xu WANG ; Jie ZHANG ; Min ZHAO ; Xiao-yu SONG ; Jian-ping DUAN
Chinese Pharmacological Bulletin 2025;41(1):171-178
Aim To explore the mechanism of Bushen Tongfu prescription(BSTF)regulating gut microbiota and improving learning and memory ability of Alzhei-mer's disease(AD)model mice.Methods APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of mice were detected by Morris water maze.The changes in the gut microbiota abundance and diversity of mice were detec-ted by 16S rDNA technology.The morphological chan-ges of hippocampus were observed by HE staining.The expression of the activation of microglia in hippocampus was detected by immunofluorescence.The expressions of pro-inflammatory factors of TLR4,NF-κB and IL-6 in brain tissue were detected by Western blot.Results Compared with the model group,the escape latency and swimming path were shortened,the times of target crossings after removing the platform increased in BSTF groups(P<0.05),the α-diversity increased and the abundance of gut microbiota was regulated,the mor-phological structure and pathological damage of hipp-ocampal cells were improved,the co-expression of iN-OS/Iba1 decreased and the co-expression of Arg1/Iba1 increased significantly(P<0.01),the transformation of M1 to M2 of microglial cells was promoted,and the expression of TLR4,NF-κB and IL-6 protein decreased significantly.Conclusions BSTF can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to regulating the gut micro-biota and the LPS/TLR4/NF-κB pathway,inhibiting the activation of pro-inflammatory microglia,reducing inflammation in hippocampus and improving the patho-logical damage of hippocampal cells.
3.Effect of immune-related genes in the prognosis of patients with head and neck squamous carcinoma
Chenxue SHI ; Min XU ; Yuxin XU ; Jian WANG ; Zhenhua WU
China Modern Doctor 2025;63(7):36-42,53
Objective To analyze the gene expression of patients with head and neck squamous cell carcinoma(HNSCC)using bioinformatics methods,identifying immune-related genes that impact prognosis and exploring new therapeutic targets for HNSCC.Methods This study was based on The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus database to download RNA sequencing data from HNSCC and non-tumor tissue samples.Differential expression gene analysis and weighted gene co-expression network analysis were performed respectively to screen immune-related genes.Univariate Cox regression,Lasso regression and multifactor Cox regression analyses were used to identify the genes significantly associated with HNSCC prognosis,and on this basis,the risk score of each TCGA sample was calculated and the correlation prognosis model was constructed.The sample was divided into high and low risk groups according to the median risk score.Gene differential expression analysis was performed in high and low risk groups to reveal gene expression changes under different immune states,and pathway enrichment analysis was performed for differential genes.Results Screening identified MS4A1,IL12RB2,DMBT1 and LTF as immune-related genes affecting the prognosis of HNSCC.Among them,MS4A1 and IL12RB2 were highly expressed in HNSCC,and DMBT1 and LTF were lowly expressed.Risk score of HNSCC death group was significantly higher than that of the survival group.Risk score could be used as an independent prognostic indicator for HNSCC.Differential genes in high and low risk groups were significantly enriched in immune response-regulating cell surface receptor signaling pathways.Conclusion MS4A1,IL12RB2,DMBT1 and LTF can be used for risk assessment,disease surveillance and efficacy evaluation of HNSCC.The immune response is crucial in the prognosis of HNSCC patients,and further studies are expected to drive the development of new therapeutic strategies.
4.Analysis of the relationship between Hp infection and the expression of p27,CyclinD1,MMP-9 proteins and the related microRNAs and clinicpathological features in gastric cancer
Jian ZHAO ; Min DAI ; Ran SUN ; Yajun XU
The Journal of Practical Medicine 2025;41(18):2890-2897
Objective To investigate the association between Helicobacter pylori(Hp)infection and the expression levels of p27,CyclinD1,matrix metalloproteinase 9(MMP-9),and related microRNAs,as well as their correlations with clinicopathological characteristics in gastric cancer(GC)tissues.Methods A total of 116 GC patients who underwent surgical resection were enrolled and classified into Hp-positive and Hp-negative groups based on Hp infection status,consisting of 76 and 40 cases,respectively.Among the Hp-positive group,patients were further categorized into good prognosis and poor prognosis subgroups according to their clinical outcomes,with 56 and 20 cases,respectively.The expression levels of p27,CyclinD1,MMP-9 proteins,as well as miR-490-3p and miR-146a in both cancerous and paracancerous tissues across the groups were compared.Additionally,the associations between the expression of these biomarkers in cancer tissues and the clinicopathological features and prognosis of Hp-positive GC patients were analyzed.Furthermore,potential risk factors contributing to poor progno-sis in Hp-positive GC patients were identified,and a predictive model was constructed to evaluate its prognostic value.Results The expression levels of p27 protein and miR-490-3p in GC tissues were significantly lower compared to those in adjacent non-cancerous tissues,whereas the expression levels of CyclinD1,MMP-9 protein,and miR-146a were significantly higher(P<0.05).In cancer tissues from the Helicobacter pylori(Hp)-positive group,the expression of p27 protein and miR-490-3p was lower than that in the Hp-negative group,while the expression of CyclinD1,MMP-9 protein,and miR-146a was higher(P<0.05).Moreover,in Hp-positive GC patients,the expression levels of p27 protein and miR-490-3p in cancer tissues were lower in those with advanced stages(Ⅲ~Ⅳ)and lymph node metastasis compared to those with early stages(Ⅰ~Ⅱ)and no lymph node metastasis(P<0.05).Conversely,the expression levels of CyclinD1,MMP-9 protein,and miR-146a were higher in patients with advanced stages and lymph node metastasis(P<0.05).Compared with the good prognosis group,the poor progno-sis group exhibited a higher proportion of advanced stages,lymph node metastasis,and elevated expression levels of CyclinD1,MMP-9 protein,and miR-146a,while the expression levels of p27 protein and miR-490-3p were reduced(P<0.05).Multivariate analysis indicated that advanced stage(Ⅲ~Ⅳ),low expression of p27 pro-tein,high expression of MMP-9 protein,and low expression of miR-490-3p were independent risk factors for poor prognosis in Hp-positive GC patients(P<0.05).The predictive model constructed for assessing the likelihood of poor prognosis in Hp-positive GC demonstrated an area under the curve(AUC)of 0.774,with a sensitivity of 80.00%and a specificity of 76.79%.Conclusions p27,CyclinD1,MMP-9 protein,miR-146a,and miR-490-3p were found to be abnormally expressed in patients with Hp-positive GC.Their expression levels were significantly associated with TNM stage and the presence of lymph node metastasis.Specifically,Stage Ⅲ~Ⅳ disease,low expression of p27 protein and miR-490-3p,and high expression of MMP-9 protein were identified as independent risk factors for poor prognosis in patients with Hp-positive GC.A predictive model based on these risk factors demonstrated favorable performance in forecasting poor clinical outcomes in this patient population.
5.A randomized,double-blind,placebo-controlled,multicenter clinical study of Shengxuebao Mixture in treating cancer-related anemia
Zhu LIU ; Xiangrong LI ; Xiaojun DAI ; Yanjun WANG ; Xiao LI ; Keqiong WANG ; Tao WU ; Miaowen ZHONG ; Hongjiang YU ; Ji FENG ; Zuowei HU ; Kainan LI ; Shaowei CHEN ; Chunhua LI ; Zhengchuan FU ; Rui ZHANG ; Yongfa CHEN ; Hongyu XU ; Tao REN ; Yibo YAO ; Jianxu JIN ; Pengyin WANG ; Zhijiang HE ; Jian SHEN ; Lei WANG ; Min LI ; Wenming CHANG ; Xinyi CHEN ; Li HOU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1447-1459
Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.
6.Construction and practice of smart health and elderly care standard system in Shanghai
Jian WANG ; Mianzhi CHENG ; Xiaohua YE ; Weihua GU ; Chun FAN ; Yuyao JIANG ; Min XU ; Yihan XU ; Yang WANG ; Xiaoyan GU ; Yihua JIANG ; Liying YAO ; Shusheng OUYANG ; Xin LIU ; Xijie YUAN ; Jian CHEN ; Ni YANG ; Qi CHEN ; Jingjing FANG
Journal of Navy Medicine 2025;46(1):83-90
With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.
7.Perioperative nursing intervention scheme for patients undergoing hepatic arterial infusion chemotherapy via brachial artery access:its construction and clinical application
Min WANG ; Jian XU ; Rui AN ; Shen ZHAO ; Ping GAO ; Jing YAN
Journal of Interventional Radiology 2025;34(10):1129-1133
Objective To construct a perioperative nursing intervention scheme for patients undergoing hepatic arterial infusion chemotherapy(HAIC)via brachial artery access and to discuss its clinical application.Methods By using systematic literature search method,a perioperative nursing intervention scheme was constructed.A total of 90 patients with confirmed hepatic malignancy,who were admitted to hospital to receive HAIC from February 2022 to August 2023,were collected to validate this perioperative nursing intervention scheme,and its clinical application effect was evaluated.Results Through two rounds of expert letter inquiry,a nursing intervention scheme containing five primary indicators and 16 secondary indicators was finally formulated.The clinical validation was conducted.After the implementation of this nursing intervention scheme,the incidences of phlebitis and limb swelling in the intervention group decreased from previous 17.78% to post-intervention 2.22% and from previous 33.33% to post-intervention 8.89%,respectively.The patient's anxiety level and depressed mood were significantly improved;the HADS scores decreased by 35.2%and 36.6%,respectively;the EORTC QLQ-C30 scores in the dimensions of somatic,role,emotional,and social functioning were obviously improved and the quality of life was strikingly improved(all P<0.05).Besides,in the patients of the intervention group the clinical symptoms(e.g.pain,nausea,etc.)were significant alleviated,and the severity of the symptoms as well as the degree of distress to the patients were significantly reduced,indicating that the nursing intervention plays an important role in relieving the symptoms,anxiety and depression of the patients.Conclusion The perioperative nursing intervention scheme constructed in this study for patients undergoing AIC via brachial artery access is scientific and practical,it provides an important reference basis for the therapeutic nursing care of patients with hepatic malignancy.
8.A randomized,double-blind,placebo-controlled,multicenter clinical study of Shengxuebao Mixture in treating cancer-related anemia
Zhu LIU ; Xiangrong LI ; Xiaojun DAI ; Yanjun WANG ; Xiao LI ; Keqiong WANG ; Tao WU ; Miaowen ZHONG ; Hongjiang YU ; Ji FENG ; Zuowei HU ; Kainan LI ; Shaowei CHEN ; Chunhua LI ; Zhengchuan FU ; Rui ZHANG ; Yongfa CHEN ; Hongyu XU ; Tao REN ; Yibo YAO ; Jianxu JIN ; Pengyin WANG ; Zhijiang HE ; Jian SHEN ; Lei WANG ; Min LI ; Wenming CHANG ; Xinyi CHEN ; Li HOU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1447-1459
Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.
9.The novel compound Austocystin R induces cycle arrest and autophagy in triple-negative breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway
Xin-yue GONG ; Min WEI ; Xiao-qin YU ; Yun-lei XU ; Yi-fan BAI ; Cheng-xiong LIU ; Fan CHENG ; Kun ZOU ; Jian-feng CHEN
Chinese Pharmacological Bulletin 2025;41(9):1651-1658
Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.
10.The novel compound Austocystin R induces cycle arrest and autophagy in triple-negative breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway
Xin-yue GONG ; Min WEI ; Xiao-qin YU ; Yun-lei XU ; Yi-fan BAI ; Cheng-xiong LIU ; Fan CHENG ; Kun ZOU ; Jian-feng CHEN
Chinese Pharmacological Bulletin 2025;41(9):1651-1658
Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

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