Omega-3 PUFAs induce apoptosis of gastric cancer cells via ADORA1.
Omega-3 PUFAs induce apoptosis of gastric cancer cells via ADORA1.
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Omega-3 PUFA 通过 ADORA1 诱导胃癌细胞凋亡。
DOI：
10.2741/4252
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Cao, Weixin
中科院分区：
文献类型：
--
作者：
Chen, Xuehua;Liu, Binya;Zhu, Zhenggang;Cao, Weixin
欧米茄-3多不饱和脂肪酸（Omega-3 PUFA），包括二十二碳六烯酸（DHA）和二十碳五烯酸（EPA），已被流行病学和临床研究表明具有抗癌作用。然而，其潜在的抗癌机制仍不清楚。在这项研究中，我们研究了两种欧米茄-3多不饱和脂肪酸（DHA和EPA）对胃癌（GC）细胞增殖和凋亡的影响，发现DHA和EPA降低了GC细胞的活力，并通过激活caspase-3诱导凋亡。此外，我们在GC细胞中筛选了DHA和/或EPA处理后的凋亡相关基因的表达谱，发现ADORA 1，一种功能性参与细胞死亡的腺苷受体亚型，响应于DHA和EPA而上调。重要的是，当用选择性ADORA 1拮抗剂DPCPX处理GC细胞时，DHA/EPA诱导的细胞凋亡显著减少。综上所述，我们的研究结果表明，ω-3多不饱和脂肪酸对胃癌的抗癌作用至少部分依赖于激活ADORA 1介导的细胞凋亡途径。
Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been suggested to have anti-cancer effects by epidemiological and clinical studies. However, their underlying anti-cancer mechanisms are still unclear. In this study, we examined the influence of two Omega-3 PUFAs (DHA and EPA) on the proliferation and apoptosis of gastric cancer (GC) cells, and found that DHA and EPA reduced the viability of GC cells and induced apoptosis by activating caspase-3. Moreover, we screened the expression profile of apoptosis-related genes in GC cells upon the treatment of DHA and/or EPA, and discovered that ADORA1, one subtype of adenosine receptor functionally involved in cell death, was up-regulated in response to DHA and EPA. Importantly, when GC cells were treated with a selective ADORA1 antagonist, DPCPX, the DHA/EPA-induced apoptosis was substantially reduced. Taken together, our results suggest that the anti-cancer effect of Omega-3 PUFAs on gastric cancer is at least partly dependent on activating the ADORA1-mediated apoptosis pathway.
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