橄榄苦苷调节PI3K/AKT信号通路对宫颈癌细胞迁移、侵袭及化疗敏感性的影响  

Effects of oleuropein on the migration,invasion,and chemotherapy sensitivity of cervical cancer cells by regulating the PI3K/AKT signaling pathway

作　　者：许丽娜[1] 温春丽[2] 郭东琳[3] 刘慧燕 王素琴[1] Xu Lina;Wen Chunli;Guo Donglin;Liu Huiyan;Wang Suqin(Department of Obstetrics and Gynecology,Shanxi Provincial People’s Hospital,Taiyuan 030012,China;Department of Traditional Chinese Medicine,Shanxi Provincial People’s Hospital,Taiyuan 030012,China;Department of Laboratory Medicine,Shanxi Provincial People’s Hospital,Taiyuan 030012,China)

机构地区：[1]山西省人民医院妇产科,太原030012 [2]山西省人民医院中医科,太原030012 [3]山西省人民医院检验科,太原030012

出　　处：《中华内分泌外科杂志（中英文）》2024年第6期892-897,共6页Chinese Journal of Endocrine Surgery

基　　金：山西省卫健委科研课题基金(2019024)。

摘　　要：目的探究橄榄苦苷(OLE)调节磷脂酰肌醇3激酶-蛋白激酶B(PI3K-AKT)信号通路对宫颈癌细胞迁移、侵袭及化疗敏感性的影响。方法采用0~80μmol/L OLE处理SiHa细胞,检测细胞存活率,筛选最佳药物浓度。将SiHa细胞随机分为SiHa组,OLE低浓度(OLE-L)组、OLE中浓度(OLE-M)组、OLE高浓度(OLE-H)组和OLE-H+PI3K激活剂740Y-P(OLE-H+740Y-P)组。采用CCK-8法检测各组细胞的增殖活性;采用Transwell实验检测各组细胞的迁移及侵袭能力;采用流式细胞术检测各组细胞凋亡率;采用免疫印迹(Western blot)检测各组细胞中PI3K-AKT信号通路相关蛋白,上皮间质转化(EMT)和耐药相关蛋白上皮钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)、N-钙黏蛋白(N-cadherin)和P-糖蛋白(P-glycoprotein,P-gp)的表达水平。结果选择浓度为5、10、20μmol/L的OLE用于后续实验;与SiHa组相比,OLE-L组、OLE-M组、OLE-H组细胞存活率、克隆形成数量、迁移及侵袭细胞数及细胞中p-PI3K/PI3K,p-AKT/AKT,Vimentin,N-cadherin和P-gp表达水平均逐渐降低(P<0.05),而细胞凋亡率和E-cadherin表达水平升高(P<0.05);相较于顺铂作用前,顺铂作用后的SiHa细胞凋亡率升高(P<0.05);在高浓度OLE的基础上加入PI3K激活剂740Y-P则逆转了以上指标的变化趋势(P<0.05)。结论OLE能抑制宫颈癌细胞的迁移、侵袭,并提高其化疗敏感性,其作用机制可能与抑制PI3K-AKT信号通路有关。ObjectiveTo investigate the effects of oleuropein(OLE)on the migration,invasion,and chemotherapy sensitivity of cervical cancer cells by regulating the phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway.MethodsSiHa cells were treated with 0-80μmol/L OLEs to detect cell survival rate and screen for the optimal drug concentration.SiHa cells were randomly separated into SiHa group,OLE low concentration(OLE-L)group,OLE medium concentration(OLE-M)group,OLE high concentration(OLE-H)group,and OLE-H+PI3K activator 740Y-P(OLE-H+740Y-P)group.CCK-8 method was applied to detect the proliferation activity of cells in each group.Transwell experiment was applied to detect the migration and invasion abilities of cells in each group.Flow cytometry was applied to detect the apoptosis rate of cells in each group.Western blot was used to detect the expression levels of PI3K-AKT signaling pathway related proteins,epithelial mesenchymal transition(EMT),and resistance related proteins such as epithelial cadherin,vimentin,N-cadherin,and P-glycoprotein(P-gp)of cells in each group.ResultsOLEs with concentrations of 5,10,and 20μmol/L were selected for subsequent experiments.Compared with the SiHa group,the survival rate,numbers of clone formation,migration and invasion of cells,and the expression levels of p-PI3K/PI3K,p-AKT/AKT,Vimentin,N-cadherin and P-gp in the OLE-L,OLE-M,and OLE-H groups gradually decreased(P<0.05),while the apoptosis rate and E-cadherin expression level increased(P<0.05).Compared to that before cisplatin treatment,the apoptosis rate of SiHa cells increased after cisplatin treatment(P<0.05).The addition of PI3K activator 740Y-P on the basis of high concentration OLE reversed the trend of changes in the above indicators(P<0.05).ConclusionsOLE can inhibit the migration and invasion of cervical cancer cells,and improve their chemotherapy sensitivity.Its mechanism of action may be related to the inhibition of the PI3K-AKT signaling pathway.

关 键 词：宫颈癌 橄榄苦苷 磷脂酰肌醇3激酶-蛋白激酶B信号通路 迁移 侵袭 化疗敏感性 

分 类 号：R285[医药卫生—中药学]