Sodium nitroprusside (SNP) sensitizes human gastric cancer cells to TRAIL-induced apoptosis.
Sodium nitroprusside (SNP) sensitizes human gastric cancer cells to TRAIL-induced apoptosis.
复制标题
硝普钠 (SNP) 使人胃癌细胞对 TRAIL 诱导的细胞凋亡敏感。
DOI：
10.1016/j.intimp.2013.06.021
复制
发表时间：
2013
影响因子：
5.6
通讯作者：
Dianchun Fang
中科院分区：
文献类型：
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作者：
Liu;C. Lan;Yu Fang;Yafei Zhang;Jun Wang;Jun Guo;Shunmei Wan;Shiming Yang;Rong;Dianchun Fang
目的探讨一氧化二氮(NO)供体硝普钠(SNP)对肿瘤坏死因子相关凋亡诱导配体(TRAIL)介导的人胃癌细胞凋亡的影响。方法采用MTT法和流式细胞术分别检测细胞增殖和凋亡标志物。通过Western blot测定caspases-8和9的表达水平。还评估了一氧化氮合酶 (NOS) 活性、NO 产生和 caspase 激活的变化。结果我们发现 TRAIL 诱导人胃癌细胞系凋亡和细胞周期停滞，并且这种效应是由 NO 产生以及细胞凋亡的外在和内在信号通路的激活介导的。此外，我们发现 NO 供体 SNP 使胃癌细胞对 TRAIL 介导的细胞凋亡敏感。用 TRAIL 和 SNP 处理细胞导致 caspase-8 和 caspase-9 的激活增加以及 NO 释放。 caspase-8 的抑制可阻断 TRAIL 诱导的细胞凋亡，而选择性 caspase-9 抑制剂无法阻止 TRAIL 或 TRAIL 加 SNP 诱导的细胞凋亡。抑制NOS可阻断caspase-9的激活，但对细胞凋亡无明显影响。结论SNP通过刺激NO的释放，使胃癌细胞对TRAIL诱导的细胞毒性敏感，进而促进线粒体介导的信号转导途径。线粒体信号通路与 TRAIL 死亡受体信号通路的结合可协同增加这些细胞的凋亡水平。
AimTo investigate the effects of the nitrous oxide (NO)-donor sodium nitroprusside (SNP) on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human gastric cancer cells.MethodsThe MTT assay and flow cytometry were used to detect cellular proliferation and markers of apoptosis, respectively. Expression levels of caspases-8, and 9 were determined by Western blot. Changes in Nitric Oxide Synthase (NOS) activity, NO production, and caspase activation were also evaluated.ResultsWe found that TRAIL induced apoptosis and cell cycle arrest in human gastric cancer cell lines, and that this effect was mediated by NO production, and activation of both the extrinsic and intrinsic signaling pathways of apoptosis. In addition, we found that the NO-donor SNP sensitizes gastric cancer cells to TRAIL-mediated apoptosis. Treatment of cells with both TRAIL and SNP resulted in increased activation of caspase-8 and caspase-9 and NO release. Inhibition of caspase-8 blocked cell TRAIL-induced apoptosis, while a selective caspase-9 inhibitor was unable to prevent apoptosis induced by either TRAIL or TRAIL plus SNP. Inhibition of NOS could block the activation of caspase-9, but had no obvious effect on cell apoptosis.ConclusionsSNP-sensitized gastric cancer cells to TRAIL-induced cytotoxicity by stimulating the release of NO, in turn facilitating the mitochondria-mediated signal transduction pathway. The engagement of the mitochondria signaling pathways along with the TRAIL death receptor signaling pathway synergistically increase levels of apoptosis in these cells.
Gomisin N 增强肿瘤坏死因子相关凋亡诱导配体 (TRAIL) 诱导的细胞凋亡
DOI：
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发表时间：
2012
期刊：
影响因子：
--
作者：
Inoue H.;Sakurai H.;Nogami N.;Fujimoto M.;Hikiami H.;Shibahara N.;Saiki I.;and Shimada Y.
通讯作者：
and Shimada Y.