Cx32通过PI3K/AKT途径调控子宫内膜癌细胞恶性生物学行为  

Cx32 regulates the malignant biological behavior of endometrial carcinoma cells through the PI3K/AKT pathway

作　　者：高珊[1] 田芃芃 韩岩书 谢驰 冯子轩 李岩[1] GAO Shan;TIAN Pengpeng;HAN Yanshu;XIE Chi;FENG Zixuan;LI Yan(Department of Obstetrics and Gynecology,Central Hospital Affiliated to Shenyang Medical College,Liaoning Shenyang 110024,China)

机构地区：[1]沈阳医学院附属中心医院妇产科,辽宁沈阳110024

出　　处：《现代肿瘤医学》2023年第16期2995-3001,共7页Journal of Modern Oncology

基　　金：沈阳医学院硕士研究生科技创新基金项目(编号:Y20210520)。

摘　　要：目的:观察间隙连接蛋白32(Cx32)与磷酸化蛋白激酶B(p-AKT)在子宫内膜癌组织与细胞系中的表达情况,以探讨Cx32通过磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/AKT)信号通路调控子宫内膜癌发生发展的相关机制。方法:采用免疫组织化学方法和Western blotting(WB)法检测子宫内膜癌组织和正常子宫内膜组织以及正常子宫内膜上皮细胞系(hEEC)和两种子宫内膜癌细胞系Ishikawa(高分化)、KLE(低分化)中的Cx32和p-AKT的表达水平,分析二者的关系。采用WB、Transwell、CCK-8和划痕愈合实验检测Cx32过表达前后各组细胞中Cx32和p-AKT的表达变化情况以及对细胞增殖、侵袭与迁移能力的影响。用PI3K/AKT信号通路抑制剂处理Cx32过表达的Ishikawa和KLE细胞,采用CCK-8法检测转染前后子宫内膜癌细胞增殖活力的变化。结果:子宫内膜癌组织中Cx32的阳性表达率(62.50%)显著低于正常子宫内膜组织中Cx32的阳性表达率(100.00%);子宫内膜癌组织中p-AKT的阳性表达率(85.00%)显著高于正常子宫内膜组织中p-AKT的阳性表达率(35.00%)(P<0.05)。Cx32与p-AKT在子宫内膜癌组织中的表达呈负相关,差异有统计学意义(r=-0.325,P<0.05)。与hEEC细胞相比,Ishikawa与KLE细胞中Cx32的表达水平降低、p-AKT的表达水平升高,KLE细胞中Cx32的表达水平最低、p-AKT的表达水平最高;Ishikawa细胞的增殖、侵袭与迁移水平显著低于KLE细胞(P<0.05)。过表达Cx32后,Cx32的表达水平升高、p-AKT的表达水平降低,细胞侵袭、迁移水平显著降低(P<0.05);经过PI3K/AKT信号通路抑制剂处理的Cx32过表达的Ishikawa和KLE细胞比未经过抑制剂处理的Cx32过表达的Ishikawa和KLE的细胞活力低(P<0.05)。结论:Cx32可以通过PI3K/AKT信号通路发挥调控子宫内膜癌发生发展的作用。与正常子宫内膜组织相比,在子宫内膜癌组织中Cx32表达降低、p-AKT表达升高;在两种癌细胞中Cx32的表达均低于正常子宫内膜上皮细胞�Objective:To observe the expression of connexin 32(Cx32)and phosphorylated protein kinase B(p-AKT)in endometrial carcinoma tissues and cell lines,in order to explore the mechanism of Cx32 regulating the occurrence and development of endometrial carcinoma(EC)through phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods:The expression levels of Cx32 and p-AKT in EC tissues and normal endometrial tissues,normal endometrial epithelial cell line(hEEC)and two EC cell lines,Ishikawa(well differentiated)and KLE(poorly differentiated),were detected by immunohistochemistry and Western blotting(WB).Analyze the relationship between the two.By WB,Transwell,CCK-8 and scratch healing,the expression changes of Cx32 and p-AKT in each group before and after Cx32 overexpression and their effects on cell proliferation,invasion and migration were measured.Cx32-overexpressed Ishikawa and KLE cells were treated with PI3K/AKT signaling pathway inhibitors,and the proliferative activity of EC cells before and after transfection was detected by CCK-8 method.Results:The positive expression rate of Cx32 in EC tissues(62.50%)was significantly lower than that in normal endometrial tissues(100.00%).The positive expression rate of p-AKT in EC tissues(85.00%)was significantly higher than that in normal endometrial tissues(35.00%)(P<0.05).Cx32 expression was negatively correlated with the expression of p-AKT in EC tissues,with statistical significance(r=-0.325,P<0.05).Compared with hEEC cells,the expression level of Cx32 in Ishikawa and KLE cells decreased and the expression level of p-AKT increased,while the expression level of Cx32 in KLE cells was the lowest and the expression level of p-AKT was the highest.The cell proliferation,invasion and migration levels of Ishikawa cells were significantly lower than those of KLE cells(P<0.05).After overexpression of Cx32,the expression level of Cx32 was increased,the expression level of p-AKT was decreased,and the level of cell invasion and migration was significantly decrease

关 键 词：子宫内膜癌 间隙连接蛋白32 磷酸化蛋白激酶B PI3K/AKT信号通路 表观遗传调控 

分 类 号：R737.33[医药卫生—肿瘤]