基于肉瘤基因信号通路探讨槲皮素对乳腺癌MCF-7细胞的作用机制
Quercetin Inhibits Breast Cancer MCF-7 Cells via RAS/RAF/MEK1 Signaling Pathway
潘小娟 1史晓光 2汪唐顺 2陈振宙 2左禧萌2
作者信息
- 1. 北京中医药大学,北京,100029
- 2. 北京中医药大学东直门医院,北京,100700
- 折叠
摘要
目的:探讨槲皮素通过RAS/RAF/MEK1信号通路对乳腺癌MCF-7细胞的作用机制.方法:将乳腺癌MCF-7细胞分为空白对照组、低剂量组、中剂量组、高剂量组、极高剂量组,采用CCK-8细胞活力检测法测定不同组别的MCF-7细胞24 h、48 h、72 h的细胞活性;采用流式细胞术检测不同组别MCF-7细胞的凋亡率;采用蛋白质印迹法检测不同组别MEK1、RAS、YAP蛋白的表达;采用免疫荧光染色观察雌激素受体、孕激素受体染色情况.结果:与空白对照组比较,低剂量组、中剂量组、高剂量组及极高剂量组的MCF-7细胞活力均出现下降,呈浓度依赖,不具有时间依赖性,差异有统计学意义(P<0.05);乳腺癌细胞MCF-7的晚期凋亡率明显增加,差异有统计学意义(P<0.05);低剂量组、中剂量组和极高剂量组MCF-7细胞的MEK1、RAS、YAP蛋白的表达出现不同程度下降,差异有统计学意义(P<0.05);低剂量组、中剂量组、高剂量组及极高剂量组的MCF-7细胞中雌激素受体、孕激素受体表达增加,差异有统计学意义(P<0.05).结论:槲皮素具有针对乳腺癌MCF-7细胞的抗肿瘤作用,且具有浓度依赖性,其机制可能与对RAS/RAF/MEK1信号通路的抑制有关.
Abstract
Objective:To investigate the mechanism of quercetin in inhibiting breast cancer Michigan cancer foundation-7(MCF-7)cells via the RAS/RAF/MEK1 signaling pathway.Methods:Breast cancer MCF-7 cells were classified into blank control and low-,medium-,high-,and extremely high-dose quercetin groups.The viability of MCF-7 cells in different groups cultured for 24,48,and 72 h were measured by the CCK-8 assay.The apoptosis rate of MCF-7 cells in different groups was determined by flow cytome-try.The protein levels of MEK1,RAS,and YAP were determined by Western blotting.Immunofluorescence staining was employed to observe the expression of estrogen receptor and progesterone receptor.Results:Compared with the blank control group,quercetin decreased the viability of MCF-7 cells in a concentration-dependent and non-time-dependent manner(P<0.05).The apoptosis rate of MCF-7 cells increased in the late stage(P<0.05).Compared with blank control group,low-,medium-,and extremely high-dose quercetin down-regulated the expression of MEK1,RAS,and YAP in MCF-7 cells(P<0.05).All the doses of quercetin promoted the expression of estrogen receptor and progesterone receptor in MCF-7 cells(P<0.05).Conclusion:Quercetin exerts a dose-de-pendent antitumor effect on breast cancer MCF-7 cells by inhibiting the RAS/RAF/MEK1 signaling pathway.
关键词
乳腺癌/RAS/RAF/MEK1信号通路/槲皮素/MCF-7细胞/细胞凋亡/雌激素受体/孕激素受体Key words
Breast cancer/RAS/RAF/MEK1 signaling pathway/Quercetin/Michigan cancer foundation-7 cells/Cell apoptosis/Estrogen receptor/Progesterone receptor引用本文复制引用
基金项目
国家自然科学基金面上项目(81973849)
北京中医药大学基本科研业务费自主选题项目(2022-BUCMXJKY009)
出版年
2023