二甲双胍抑制赖氨酸特异性组蛋白去甲基化酶1介导的卵巢癌细胞增殖和迁移

目的: 探讨二甲双胍抑制卵巢癌细胞增殖和迁移的可能分子机制。方法: 用不同浓度二甲双胍(0、5、10和20 mmol/L)处理卵巢癌HO8910和SKOV3细胞，EdU和迁移实验检测细胞增殖和迁移能力；免疫印迹和qRT-PCR检测细胞内赖氨酸特异性组蛋白去甲基化酶1(lysine specific demethylase 1，LSD1)蛋白及mRNA表达水平；免疫印迹检测PI3K/AKT信号通路蛋白表达水平。建立诱导型稳定敲低LSD1的卵巢癌HO8910和SKOV3细胞株，经10 mmol/L二甲双胍处理，通过EdU和迁移实验检测各组细胞增殖和迁移能力。结果： 与对照组相比，不同浓度二甲双胍处理组细胞增殖和迁移能力明显降低(P均＜0.01)，LSD1蛋白表达水平明显降低，LSD1特异性底物H3K4me2蛋白表达水平明显升高(P均＜0.01)；PI3K/AKT信号通路蛋白PI3K和p AKT表达水平明显降低(P均＜0.01)。二甲双胍处理和敲低LSD1后，细胞增殖和迁移能力均显著降低（P<0.05)。结论： 二甲双胍可能通过抑制PI3K/AKT通路下调LSD1蛋白表达，从而抑制卵巢癌细胞增殖与迁移。

Metformin inhibits LSD1-mediated proliferation and migration of ovarian cancer cells

Objective: To investigate the molecular mechanism of metformin in inhibiting the proliferation and migration of ovarian cancer cells.  Methods: Ovarian cancer HO8910 and SKOV3 cells were treated with metformin at different concentrations(0, 5, 10, and 20 mmol/L), cell proliferation and migration ability were measured by EdU and migration assays, lysine specific demethylase 1(LSD1) protein and mRNA expression levels were detected by Western blotting and qRT PCR, the protein expression level of PI3K/AKT signaling pathway was detected by Western blotting. In addition, inducible stable knockdown of LSD1 ovarian cancer HO8910 and SKOV3 cell lines were established, and the effects of metformin treatment and LSD1 knockdown on the proliferation and migration of ovarian cancer cells were measured by EdU and migration assays. Results: Compared with the control group, the cell proliferation and migration ability of the metformin treatment groups were significantly reduced(all P<0.01). The expression level of LSD1 protein was significantly reduced, and the protein level of H3K4me2, a specific substrate of LSD1, was significantly increased (all P<0.01). The protein expression levels of PI3K and p AKT in PI3K/AKT signaling pathway were significantly reduced (all P<0.01). After metformin treatment and LSD1 knockdown, the cell proliferation and migration ability were significantly reduced(P<0.05）. Conclusion: Metformin may inhibit the proliferation and migration of ovarian cancer cells by down regulating LSD1 protein expression via inhibiting the PI3K/AKT pathway.