桔梗皂苷D介导PI3K/AKT/mTOR信号通路调控子宫内膜癌细胞株ECC-1增殖、侵袭和迁移  

Effect of platycodin D on proliferation, invasion and migration of endometrial cancer cell line ECC-1 through PI3K/AKT/m TOR signaling pathway

作　　者：鲍慧 孙晓东[1] 乔健[1] 贺晶[2] BAO Hui;SUN Xiaodong;QIAO Jian;HE Jing(No.2 Ward,Department of Oncology,Yan'an University Affiliated Hospital,Yan'an,Shaanxi 716000,China;Department of Gynecology,Yan'an University Affiliated Hospital,Yan'an,Shaanxi 716000,China)

机构地区：[1]延安大学附属医院肿瘤科二病区,陕西延安716000 [2]延安大学附属医院妇科,陕西延安716000

出　　处：《中国优生与遗传杂志》2022年第9期1524-1530,共7页Chinese Journal of Birth Health & Heredity

基　　金：北京医卫健康公益基金会《医学科学研究基金资助项目》(YWJKJJHKYJJ-F1051B)。

摘　　要：目的 探讨桔梗皂苷D介导磷酸肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路调控子宫内膜癌细胞株ECC-1增殖、侵袭和迁移作用。方法 将人子宫内膜癌细胞株ECC-1分为对照组,桔梗皂苷D低、中、高剂量组(9μmol/L、18μmol/L、36μmol/L),PI3K抑制剂(PQR309)组(1μmol/L),PI3K激动剂(IGF-1)组(100 mg/L)。培养48 h后,四甲基偶氮唑蓝、侵袭小室和划痕实验分别检测细胞增殖、侵袭和迁移活性;实时定量聚合酶链反应和蛋白免疫印迹法检测细胞PI3K、AKT、mTOR、c-Myc、细胞周期蛋白激酶6(CDK6)、E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)、锌指转录因子(Snail)信使核糖核酸(mRNA)和蛋白表达及p-PI3K、p-AKT、p-mTOR水平。结果 与对照组比,IGF-1组细胞侵袭细胞数和细胞划痕愈合率上升,PI3K、AKT、mTOR mRNA和蛋白表达及p-PI3K、p-PI3K/PI3K、p-AKT、p-AKT/AKT、p-mTOR、p-mTOR/mTOR水平、c-Myc、CDK6、Vimentin、Snail mRNA和蛋白表达增加,差异有统计学意义(P<0.05)。PQR309组和桔梗皂苷D 3剂量组细胞增殖抑制率上升、E-cadherin mRNA和蛋白表达增加,差异有统计学意义(P<0.05);上述指标PQR309组和桔梗皂苷D中剂量组细胞差异无统计学意义(P>0.05);上述指标桔梗皂苷D呈剂量依赖性。结论 桔梗皂苷D抑制子宫内膜癌细胞增殖侵袭和迁移,可能与抑制PI3K/AKT/mTOR信号通路,抑制c-Myc、CDK6、Vimentin、Snail表达,促进E-cadherin表达相关。Objective To investigate the effect of platycodin D mediated phosphoinositol-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling pathway on the proliferation, invasion and migration of endometrial cancer cell lines ECC-1. Methods Human endometrial cancer cell lines ECC-1 were divided into control group,low, medium and high dose platycodin D groups, PI3K inhibitor(PQR309) group, PI3K agonist(IGF-1) group. After 48 h culture, the proliferation activities, cell invasion activities, cell migration activities of each group were detected by methyl thiazolyl tetrazolium assay, Transwell chamber assay, scratch assay, and real-time quantitative polymerase chain reaction was used to detect PI3K, AKT, mTOR, c-Myc, cyclin dependent kinase 6(CDK6), E-cadherin, Vimentin, zinc finger transcription factor(Snail) messenger RNA(mRNA) expressions in each group, and the protein expressions of PI3K, AKT, mTOR, p-PI3K,p-AKT, p-mTOR, levels were detected by western blotting. Results Compared with the control group, the number of invasive cells and the healing rate of scratch were increased, mRNA and protein expressions of PI3K, AKT, mTOR, and the levels of p-PI3K, p-PI3K/PI3K, p-AKT, p-AKT/AKT, p-mTOR p-mTOR/mTOR, c-Myc, CDK6, Vimentin, snail mRNA and protein expressions increased in IGF-1 group, with statistical significance(P<0.05), and cell proliferation inhibition rate of PQR309group and platycodin D 3 dose groups were increased, and E-cadherin mRNA and protein expression were increased, with statistical significance(P<0.05). There was no significant difference between PQR309 group and platycodin D medium dose group(P>0.05). The indexes of platycodin D were dose dependent. Conclusion Platycodin D inhibits the proliferation, invasion and migration of endometrial cancer cells, which may be related to the inhibition of PI3K/AKT/mTOR signaling pathway and the expression of c-MyC, CDK6, Vimentin and Snail, and the promotion of E-cadherin.

关 键 词：桔梗皂苷D 子宫内膜癌 PI3K/AKT/mTOR信号通路 增殖 转移 

分 类 号：R285[医药卫生—中药学]