银杏内酯K调节AMPK/mTOR/ULK1信号通路对乳腺癌细胞自噬和凋亡的影响

目的 探讨银杏内酯K（GK）调节AMPK/mTOR/ULK1信号通路对乳腺癌细胞自噬和凋亡的影响。方法 取对数生长期的MCF-7细胞，设置分组为对照组、GK低浓度（GK-L，12.5 μg/mL）组、GK中浓度（GK-M，25 μg/mL）组、GK高浓度（GK-H，50 μg/mL）组、GK-H+AMPK抑制剂（Compound C，50 μg/mL GK+50 μmol/L Compound C）组。观察各组细胞形态以及细胞增殖、凋亡、自噬状况并分析自噬相关基因LC3、P62、Beclin1 mRNA表达以及AMPK、p-mTOR、mTOR、p-ULK1、ULK1、LC3、P62、Beclin1表达。结果 与对照组相比，GK-L、GK-M、GK-H组细胞自噬泡数量增多，增殖率、p-mTOR/mTOR、p-ULK1/ULK1、p62表达显著下降，凋亡率、LC3、Beclin1表达、AMPK蛋白表达显著增加（P＜0.05）；与GK-H组相比，GK-H+Compound C组细胞自噬泡数量减少，增殖率、p-mTOR/mTOR、p-ULK1/ULK1、p62显著增加，凋亡率、LC3、Beclin1表达、AMPK蛋白表达显著降低（P＜0.05）。结论 GK可以诱导乳腺癌细胞自噬和凋亡、抑制其增殖，可能与激活AMPK/mTOR/ULK1信号通路有关

Influences of ginkgolide K on autophagy and apoptosis in breast cancer cells by regulating AMPK/mTOR/ULK1 signaling pathway

Objective To investigate the influences of ginkgolide K (GK) on autophagy and apoptosis in breast cancer cells by regulating AMPK/mTOR/ULK1 signaling pathway. Methods MCF-7 cells in the logarithmic growth phase were taken and grouped into control group, GK low concentration (GK-L, 12.5 μg/mL) group, GK medium concentration (GK-M, 25 μg/mL) group, GK high concentration (GK-H, 50 μg/mL) group, G -H+AMPK inhibitor (Compound C, 50 μg/mL GK+50 μmol/L Compound C) group. The cell morphology, cell proliferation, apoptosis and autophagy were observed, and the mRNA expressions of autophagy-related genes LC3, P62 and Beclin1, as well as the expressions of AMPK, p-mTOR, mTOR, p-ULK1, ULK1, LC3, P62 and Beclin1 were analyzed. Results Compared with the control group, the number of autophagic vesicles in the GK-L, GK-M and GK-H groups increased, the proliferation rate, and the expression of p-mTOR/mTOR, p-ULK1/ULK1 and p62 decreased significantly, the apoptosis rate, the expression of LC3, Beclin1, and the expression of AMPK protein increased significantly (P<0.05); compared with the GK-H group, the number of autophagic vesicles in the GK-H+Compound C group decreased, the proliferation rate, and the expression of p-mTOR/mTOR, p-ULK1/ULK1 and p62 increased significantly, the apoptosis rate, the expression of LC3, Beclin1, and the expression of AMPK protein decreased significantly (P<0.05). Conclusion GK can induce autophagy and apoptosis and inhibit the proliferation of breast cancer cells, which may be related to the activation of AMPK/mTOR/ULK1 signaling pathway