他莫昔芬对ER- GPER+乳腺癌细胞上皮间质转化的影响及机制

目的：探讨他莫昔芬（TAM）对雌激素受体（ER）阴性、G蛋白偶联雌激素受体（GPER）阳性乳腺癌细胞上皮间质转化（EMT）的影响。方法：以ER阴性（ER-）、GPER阳性（GPER+）乳腺癌MDA-MB-468细胞为研究对象，用TAM处理细胞，GPER特异性抑制剂G15抑制胞内GPER活性，siRNA干扰GPER蛋白表达，侵袭小室实验检测细胞侵袭能力，Western blot检测ERα、GPER、Vimentin、E-cadherin及N-cadherin蛋白表达变化。结果：TAM（5 μmol/L）可明显增强MDA-MB-468细胞的侵袭能力（P＜0.01）；G15（10 μmol/L）预处理能显著抑制TAM诱导的细胞侵袭活动（P＜0.01）；GPER-siRNA可明显干扰MDA-MB-468细胞GPER蛋白表达（P＜0.01）；干扰GPER蛋白表达能有效抑制TAM诱导的细胞侵袭活动（P＜0.01）。TAM处理明显诱导Vimentin和N-cadherin蛋白表达上调（P＜0.01），E-cadherin蛋白表达下调（P＜0.01）；G15预处理或干扰GPER蛋白表达均能抑制TAM的上述诱导作用（均P＜0.05）。结论：TAM能诱导ER- GPER+乳腺癌MDA-MB-468细胞EMT，其作用与其激活GPER有关。

The effect of tamoxifen on ER- GPER+ breast cancer cell EMT and its mechanism

Objective: To investigate the effect of TAM on EMT in ER- GPER+ breast cancer cells and to discuss its signaling mechanism. Methods: ER- GPER+ breast cancer MDA-MB-468 cells were researched object. Cells were treated by TAM, intracellular GPER activity were inhibited by GPER specific inhibitor G15, GPER protein expression was interfered by siRNA , cell invasion ability was detected by invasion chamber experiment and western blot experiment was used to detect ERα, GPER, Vimentin, E-cadherin and N-cadherin protein expression changes. Results: TAM (5 μmol/L) could significantly enhance the invasion ability of MDA-MB-468 cells (P<0.01), and G15 (10 μmol/L) pretreatment could significantly inhibit TAM-induced cell invasion (P<0.01). GPER-siRNA could significantly interfere with the expression of GPER protein in MDA-MB-468 cells (P<0.01), and interference with GPER protein expression could effectively inhibit TAM-induced cell invasion (P<0.01). TAM treatment significantly induced up-regulation of Vimentin and N-cadherin protein expression (P<0.01) and down-regulation of E-cadherin protein expression (P<0.01). G15 pretreatment or interference with GPER protein expression could inhibit the above induction of TAM (P<0.05). Conclusion: TAM can induce EMT in ER-GPER+ breast cancer MDA-MB-468 cells, which is related to the activation of GPER.