Resveratrol induces apoptosis, autophagy and endoplasmic reticulum stress in colon cancer cells

Hao-wei Jia, Yue Wu, Ruixin Li, Hongchao Zhao, Guojun Wang, Junfeng Sun
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引用次数: 5

Abstract

Objective : Resveratrol exerts various biologic effects. This study was designed to investigate its anti-cancer effect and its impact on cell apoptosis, autophagy, and endoplasmic reticulum stress (ER-stress) in colon cancer. Methods : Colon cancer cells were treated with resveratrol. Cell viability, apoptosis, and autophagy were assessed by MTT, flow cytometry, and green fluorescence protein (GFP)-tagged LC3B analysis, respectively. Gene expression was detected by qRT-PCR and western blot. Xenograft model was subjected to verify the effects of resveratrol on tumorigenesis of colon cancer cells in vivo. Results : The viability of colon cancer cells was reduced by resveratrol. The cell apoptosis and the protein levels of apoptotic markers (cleaved-PARP and cleaved-Caspase3) were increased by resveratrol. The protein level of autophagic marker (MAP1LC3B) and the LC3B dots accumulation were elevated by resveratrol. Autophagy inhibitor (3-MA) partially reversed the effect of resveratrol on cell apoptosis. The protein and mRNA levels of ER-stress markers (IRE-1 and ATF6) and pro-apoptotic signals (GRP-78, GADD153) were up-regulated by resveratrol. The tumor growth of colon cancer cells was suppressed by resveratrol in vivo. Conclusion : Resveratrol exerts anti-cancer function of colon cancer, which is associated with its induction effect of cell apoptosis, autophagy and ER-stress. Keywords: resveratrol; colon cancer; apoptosis; autophagy; endoplasmic reticulum stress
白藜芦醇诱导结肠癌细胞凋亡、自噬和内质网应激
目的:白藜芦醇具有多种生物效应。本研究旨在探讨其抗癌作用及其对结肠癌细胞凋亡、自噬和内质网应激(er -应激)的影响。方法:用白藜芦醇处理结肠癌细胞。通过MTT、流式细胞术和绿色荧光蛋白(GFP)标记LC3B分析分别评估细胞活力、凋亡和自噬。采用qRT-PCR和western blot检测基因表达。采用异种移植模型验证白藜芦醇对结肠癌细胞体内肿瘤发生的影响。结果:白藜芦醇可降低结肠癌细胞活力。白藜芦醇可促进细胞凋亡及凋亡标志物(裂解- parp和裂解- caspase3)蛋白水平升高。白藜芦醇可提高自噬标志物(MAP1LC3B)蛋白水平和LC3B圆点积累。自噬抑制剂(3-MA)部分逆转了白藜芦醇对细胞凋亡的影响。白藜芦醇上调内质网应激标志物(IRE-1、ATF6)和促凋亡信号(GRP-78、GADD153)的蛋白和mRNA水平。白藜芦醇在体内可抑制结肠癌细胞的肿瘤生长。结论:白藜芦醇具有结肠癌的抗癌作用,其作用机制与其诱导细胞凋亡、自噬和内质网应激有关。关键词:白藜芦醇;结肠癌;细胞凋亡;自噬;内质网应激
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