雌激素跨膜受体GPR30介导子宫内膜癌中IL-6/STAT3炎症信号通路的激活

目的:探讨新型雌激素跨膜受体GPR30对子宫内膜癌中IL-6/STAT3炎症信号通路的调节作用。方法:将子宫内膜癌细胞系Ishikawa、KLE分为5组:对照组、E2组、G1组(GPR30特异性激动剂)、E2+G15组(GPR30特异性抑制剂)、G1+G15组。应用转染技术下调Ishikawa和KLE细胞中GPR30的表达后,分别给予E2和G1作用。Western blot法检测各组细胞中STAT3的蛋白表达水平;ELISA法检测细胞培养上清中IL-6的含量。结果:Ishikawa、KLE细胞系中E2组和G1组的STAT3蛋白及IL-6表达水平均显著高于对照组、E2+G15组、G1+G15组(P<0.05)。GPR30稳定下调后,E2+RNAi组和G1+RNAi组中STAT3蛋白与IL-6表达上调均被阻断(P<0.05)。结论:E2和G1能促进子宫内膜癌细胞中IL-6/STAT3的表达,GPR30的表达下调和阻滞剂能抑制E2和G1诱导的子宫内膜癌细胞IL-6/STAT3的表达。GPR30可通过激活IL-6/STAT3炎症通路而在子宫内膜癌组织中发挥重要作用。

Study on the expression of IL-6/STAT3 in endometrial cancer cells mediated by GPR30

Objective:To study the expression of IL-6/STAT3 in endometrial carcinoma cell lines mediated by G-protein coupled receptor 30(GPR30).Methods:The endometrial cancer cell lines Ishikawa and KLE were divided into 5 groups:Con,E2,G1,E2+G15(GPR30 specific antagonist),G1+G15.The expression of GPR30 was downregulated in endometrial cancer cells by transfection with shGPR30-pGFP-V-RS,a GPR30 antisense expression vector.The protein expression level of STAT3 in each group was determined by Western blot.The expression level of IL-6 was detected by ELISA.Result:The expression of STAT3 and the secretion of IL-6 in E2 and G1 group were significantly higher than those in the control group,E2+G15 and G1+G15 group(P<0.05).Inhibition of GPR30 by RNA interference could reduce the expression of STAT3 and the secretion of IL-6 in E2 and G1 group.Conclusions:The E2 and G1 can promote the expression of IL-6/STAT3 in endometrial cancer cells.Downregulation of GPR30 can inhibit the expression of IL-6/STAT3 induced by E2 and G1 in endometrial cancer cells.Estrogen transembrane receptor GPR30 plays an important role in endometrial carcinoma by regulating the expression of IL-6/STAT3.