槲皮素对胃癌相关p53/AMPK/mTOR信号通路的影响

目的　探讨槲皮素（QE）对胃癌相关p53/AMPK/mTOR信号通路的影响。方法　将胃癌细胞分为QE组和溶剂组，QE组以DMSO为溶剂按配制QE浓度分别为0.02、0.04、0.06及0.08 mmol/L，对细胞进行干预，分别为QEA、QEB、QEC、QED组，溶剂组加入等量不含QE的溶剂。MTT实验检测槲皮素对胃癌细胞增殖的影响；MDC染色法检测槲皮素对胃癌细胞自噬的影响；双染法检测槲皮素对胃癌细胞凋亡的影响；实时荧光定量聚合酶链反应检测细胞内p53、AMPK及mTOR的mRNA相对表达水平；Western blot检测细胞内LC3Ⅱ/LC3Ⅰ、P53、AMPK、mTOR蛋白表达差异。结果　与溶剂组相比，QE各剂量组胃癌细胞的自噬程度和凋亡率均显著增加，细胞中LC3Ⅱ/Ⅰ蛋白表达量上调，p53、AMPK mRNA和蛋白水平均上调，mTOR的mRNA和蛋白表达量均下调（P＜0.05），且呈剂量依赖性。结论　QE可以抑制胃癌细胞增殖，诱导其发生自噬、促进其凋亡，其作用机制可能与p53/AMPK/mTOR信号通路有关。

Effects of quercetin on p53/AMPK/mTOR signaling pathway related to gastric cancer

Objective　To explore the effect of quercetin (QE) on gastric cancer-related p53/AMPK/mTOR signaling pathway. Methods　Gastric cancer cells were divided into the QE group and the solvent group. DMSO was used as the solvent. QE was formulated into 0.02 (QEA group), 0.04 (QEB group), 0.06 (QEC group), and 0.08 mmol/L (QED group) solutions. The solvent group was added the same amount of solvent without QE. MTT test was used to detect the effect of quercetin on gastric cancer cell proliferation. MDC staining method was used to detect the effect of quercetin on gastric cancer cell autophagy. Double staining method was used to detect the effect of quercetin on gastric cancer cell apoptosis. Real-time polymerase chain reaction test was used to detect the relative expression levels of p53, AMPK and mTOR mRNA in cells. Western blot assay was used to detect the differences in the expression levels of LC3Ⅱ/LC3Ⅰ, P53, AMPK and mTOR in cells. Results　Compared with the solvent group, the autophagy and apoptosis rate of gastric cancer cells were significantly increased in the different QE dose groups (P＜0.05). The expression of LC3Ⅱ/LC3Ⅰ protein in cells was up-regulated in the QE groups, and p53, AMPK mRNA and protein levels were also up-regulated, and the mRNA and protein expression of mTOR were down-regulated (P＜0.05) with a dose-dependent pattern. Conclusion　Quercetin can inhibit the proliferation of gastric cancer cells, induce autophagy and promote apoptosis, which may be related to the p53/AMPK/mTOR signaling pathway.