E-钙粘素介导的细胞粘附通过EGFR激活卵巢癌细胞PI3K-Akt信号通路  

Activation of phosphatidylinositol 3 kinase (PI3K)/Akt signaling transduction pathway induced by E-cadherin-mediated cell-cell adhesion through epidermal growth factor receptor in ovarian cancer cells

作　　者：刘联[1] 张昕[1] 王秀问[1] 黎莉[1] 于学军[1] 徐从高[1] 

机构地区：[1]山东大学齐鲁医院肿瘤中心,济南250012

出　　处：《现代妇产科进展》2007年第4期270-273,共4页Progress in Obstetrics and Gynecology

摘　　要：目的研究E-钙粘素介导的细胞粘附对卵巢癌细胞Akt及其上游的磷脂酰肌醇3-激酶(phosphatidylinositol 3-Kinase,PI3K)信号的激活及对卵巢癌细胞增殖的作用。方法基于卵巢癌细胞株CaOV-3构建Ca2+依赖性细胞粘附模型;Western blot和免疫沉淀法检测E-钙粘素介导的细胞粘附通过表皮生长因子受体(epidermal growth factor recep-tor,EGFR)对PI3K-Akt的激活;同时通过阻断该通路的关键组分观察对卵巢癌细胞增殖的影响。结果(1)E-钙粘素介导的细胞粘附可激活卵巢癌细胞内部的EGFR-PI3K-Akt信号通路;(2)应用E-钙粘素抗体或PI3K抑制剂处理的CaOV-3细胞株表现出生长受阻的现象,72h时细胞生长抑制率分别达73.5%和78.8%。结论E-钙粘素激活卵巢癌细胞EGFR-PI3K-Akt相关的信号转导通路对肿瘤细胞的增殖有重要作用。干预该信号通路的关键组分显著抑制细胞生长,为卵巢癌的靶向治疗提供了新的有价值的干预靶点。Objective：To study the activation of Akt and its upstream molecule, phosphatidylinositol 3 kinase （PI3 K） induced by E-cadherin-mediated cell-cell adhesion and their effect on ovarian cancer cell proliferation. Methods：A calcium-dependent cell adhesion model based on ovarian cancer cell line CaOV-3 was established. The function of E-cadherin-mediated cell-cell adhesion to activate PI3K-Akt through epidermal growth factor receptor （EGFR） was detected with Western blot and immunoprecipitation, and its influences on cell growth were detected by blocking functions of certain components on the pathway with their inhibitors, respec- tively. Results： （1） E-cadherin-mediated cell-cell adhesion activated EGFR and downstream PI3K/Akt in CaOV-3 cells. （2） Suppression of E-cadherin or PI3K function resulted in retarded cell proliferation. The inhibiting rates were 73.5% and 78.8% respectively after 72 hours of incubation. Conclusion： The activation on EGFR-PI3K-Akt cascade by E-cadherin mediated cell adhesion plays a major role in ovarian cell proliferation. Interference on key components in this signaling pathway may lead to marked inhibition of cell growth, which implies a new promising target for targeted therapies for ovarian cancers.

关 键 词：卵巢肿瘤 E-钙粘素 磷脂酰肌醇3-激酶 受体 表皮生长因子 细胞粘附 信号转导 

分 类 号：R737.33[医药卫生—肿瘤]