中药新药与临床药理2025,Vol.36Issue(6):852-858,7.DOI:10.19378/j.issn.1003-9783.2025.06.002
淫羊藿苷调控Src/FAK通路影响卵巢癌细胞顺铂耐药性的作用机制
Mechanism of Icariin Regulating Src/FAK Pathway Affecting Cisplatin Resistance in Ovarian Cancer Cells
摘要
Abstract
Objective To investigate the effect of icariin on cisplatin(DDP)resistance in ovarian cancer cells based on the steroid receptor coactivator(Src)/focal adhesion kinase(FAK)pathway.Methods Cisplatin-resistant SKOV3 cells(SKOV3/DDP)were constructed by gradually increasing the concentration of cisplatin.The optimal intervention concentrations of icariin and cisplatin were determined by CCK-8 assay to measure cell proliferation rate.SKOV3/DDP cells were divided and intervened as follows:the control group received no intervention;the cisplatin group was treated with 5 µg·mL-1 cisplatin for 24 hours;the cisplatin+icariin group was treated with 5 µg·mL-1 cisplatin and 20 µg·mL-1 icariin simultaneously for 24 hours;the cisplatin+sc-3052 group was treated with 5 µg·mL-1 cisplatin and 3 µmol·L-1 sc-3052 simultaneously for 24 hours;the cisplatin+icariin+sc-3052 group was treated with 5 µg·mL-1 cisplatin,20 µg·mL-1 icariin,and 3 µmol·L-1 sc-3052 simultaneously for 24 hours.The absorbance(A450)value of cells was detected by CCK-8 assay;cell proliferation ability was assessed by colony formation assay;cell invasion ability was evaluated by Transwell assay;cell migration ability was measured by scratch assay;cell apoptosis was detected by flow cytometry;and the protein levels of multidrug resistance-associated protein 5(MRP5),multidrug resistance protein 1(MDR1),p-Src,p-FAK,and phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)in SKOV3/DDP cells were determined by Western Blot.Results(1)SKOV3 cells that could stably grow in 5 µg·mL-1 cisplatin were collected as SKOV3/DDP.The concentrations of 20 µg·mL-1 icariin and 5 µg·mL-1 cisplatin were selected for subsequent experiments.(2)Compared with the control group,there were no significant differences in the above detection indicators in the cisplatin group(P>0.05).Compared with the cisplatin group,the A450 value,colony formation rate,number of invasive cells,scratch healing rate,and protein expression levels of MRP5,MDR1,p-Src,p-FAK,and p-ERK1/2 in the cisplatin+icariin group were significantly decreased(P<0.05),while the apoptosis rate was significantly increased(P<0.05).In the cisplatin+sc-3052 group,the A450 value,colony formation rate,number of invasive cells,scratch healing rate,and protein expression levels of MRP5,MDR1,p-Src,p-FAK,and p-ERK1/2 were significantly increased(P<0.05),while the apoptosis rate was significantly decreased(P<0.05).Compared with the cisplatin+icariin group,the A450 value,colony formation rate,number of invasive cells,scratch healing rate,and protein expression levels of MRP5,MDR1,p-Src,p-FAK,and p-ERK1/2 in the cisplatin+icariin+sc-3052 group were significantly increased(P<0.05),while the apoptosis rate was significantly decreased(P<0.05).Conclusion Icariin may reduce cisplatin resistance in SKOV3/DDP cells by inhibiting the Src/FAK pathway.关键词
淫羊藿苷/卵巢癌/顺铂耐药性/SKOV3 细胞/类固醇受体共激活因子/黏着斑激酶通路Key words
icariin/ovarian cancer/cisplatin resistance/SKOV3 cells/steroid receptor coactivator/focal adhesion kinase pathway分类
医药卫生引用本文复制引用
韩江红,王文翔,罗欢欢,王孟琪..淫羊藿苷调控Src/FAK通路影响卵巢癌细胞顺铂耐药性的作用机制[J].中药新药与临床药理,2025,36(6):852-858,7.基金项目
2021年度河南省医学科技攻关计划联合共建项目(LHGJ20210914). (LHGJ20210914)