Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells
Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells
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DOI：
10.1080/10286020.2014.951923
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发表时间：
2015-01-02
影响因子：
1.7
通讯作者：
Yin, Pei-Hao
中科院分区：
文献类型：
--
作者：
Cao, Ai-Li;Tang, Qing-Feng;Yin, Pei-Hao
姜黄素是从姜黄根茎中提取的具有生物活性的化合物，能抑制胃癌细胞的生长并诱导其凋亡。但姜黄素对胃癌细胞的作用机制仍需进一步研究。形态学观察结果表明，姜黄素对AGS细胞的增殖有抑制作用，并呈剂量依赖性。流式细胞仪分析显示，姜黄素处理后AGS细胞出现G2/M期阻滞，细胞周期蛋白B1表达增加，D1表达减少。凝胶电泳观察到DNA梯状条带。同时，姜黄素处理的AGS细胞caspase-3、caspase-8和caspase-9的活性也增强。然而，苄氧羰基-Val-Ala-Asp（OME）-氟甲基酮（z-VAD-factorylketone，z-VAD-factorylketorylket Western blot结果显示姜黄素处理后AGS细胞Ras表达下调，ERK表达上调。ERK抑制剂U 0126可阻断姜黄素诱导的细胞凋亡。结果提示，姜黄素通过激活Ras/ERK信号通路及下游caspase级联反应抑制AGS细胞生长并诱导其凋亡，姜黄素可能成为胃癌治疗的潜在靶点。
Curcumin, the biologically active compound from the rhizome of Curcuma longa, could inhibit cell growth and induce apoptosis in gastric carcinoma. However, the underlying mechanism of curcumin on gastric carcinoma cells still needs further investigation. In this study, morphological observation indicated that curcumin inhibited the proliferation of AGS cells in a dose-dependent manner. According to the flow cytometric analysis, curcumin treatment resulted in G2/M arrest in AGS cells, accompanied with an increased expression of cyclin B1 and a decreased expression of cyclin D1. In addition, DNA ladders were observed by gel electrophoresis. Meanwhile, the activities of caspase-3, -8, and -9 were also enhanced in curcumin-treated AGS cells. Nevertheless, the increased activities could be inhibited by benzyloxycarbonyl-Val-Ala-Asp (OME)-fluoromethylketone (z-VAD-fmk), which suggested that the apoptosis was caspase-dependent. Furthermore, downregulation of rat sarcoma (Ras) and upregulation of extracellular-signal-regulated kinase (ERK) were also observed in AGS cells treated with curcumin by Western blot. U0126, an ERK inhibitor, blocked curcumin-induced apoptosis. The results suggested that curcumin inhibited the growth of the AGS cells and induced apoptosis through the activation of Ras/ERK signaling pathway and downstream caspase cascade, and curcumin might be a potential target for the treatment of gastric carcinoma.