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雌激素活化GPER介导的IL-6/STAT3通路促进乳腺癌细胞SKBR-3增殖作用

, PP. 340-345

Keywords: GPER,雌激素,IL-/STAT信号通路,细胞增殖

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Abstract:

目的探讨雌激素活化膜性雌激素受体(G-proteincoupledestrogenreceptor,GPER)所介导的IL-6/STAT3炎症信号通路对乳腺癌SKBR-3细胞增殖能力的影响。方法用17-β雌二醇(E2)、GPER特异性激动剂(G1)、GPER特异性拮抗剂(G15)、IL-6中和抗体(Anti-IL-6)及STAT3特异性抑制剂JSI-124(cucurbitacinI)药物处理SKBR-3细胞后,分别得到对照组、E2处理组、G1处理组、E2+G15处理组、G1+G15处理组、E2+Anti-IL-6处理组、G1+Anti-IL-6处理组、E2+JSI-124处理组与G1+JSI-124处理组,用ELISA检测细胞培养液上清中IL-6的分泌量,CCK-8法检测细胞增殖能力的变化,Westernblot检测细胞中p-STAT3与STAT3的蛋白表达水平。结果E2和G1显著促进SKBR-3细胞上清中IL-6的分泌量,G15可显著阻断其分泌(P<0.05)。E2及G1药物处理细胞后增殖能力较对照组显著增强,相对细胞数分别为对照组的(1.68±0.13)倍与(1.74±0.21)倍,其促增殖作用被G15及IL-6中和抗体(Anti-IL-6)显著抑制(P<0.05)。E2及G1在不同时间点(1、3、6、12h)均可显著促进细胞中p-STAT3的蛋白表达量,分别于12h和3h达到表达峰值,其蛋白相对表达量分别为对照组的(2.54±0.23)倍和(3.12±0.24)倍。G15、Anti-IL-6及JSI-124显著阻断以上变化(P<0.05)。JSI-124亦可明显抑制E2及G1所引起的促增殖效应(P<0.05)。结论雌激素活化膜性雌激素受体GPER促进乳腺癌SKBR-3细胞自分泌IL-6从而激活细胞中下游STAT3炎症信号通路,同时,GPER/IL-6/STAT3信号通路也介导了雌激素对细胞的增殖作用。

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