Helicobacter pylori infection induces apoptosis in gastric cancer cells through the mitochondrial pathway
Helicobacter pylori infection induces apoptosis in gastric cancer cells through the mitochondrial pathway
复制标题
幽门螺杆菌感染通过线粒体途径诱导胃癌细胞凋亡
DOI：
10.1111/j.1440-1746.2007.04959.x
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发表时间：
2007-07-01
影响因子：
4.1
通讯作者：
Luo, Yuan-Hui
中科院分区：
文献类型：
--
作者：
Zhang, Hao;Fang, Dian-Chun;Luo, Yuan-Hui
背景和目的：探讨线粒体途径在H.方法：将胃腺癌细胞系SGC-7901与H. pylori NCTC 11637，用或不用半胱天冬酶-3、-8和-9抑制剂预孵育。流式细胞术检测细胞凋亡。RT-PCR检测Bid、Bax、Bcl-2 mRNA的表达，Western blotting检测Bid、Bax、Bcl-2蛋白的表达及caspase-3、-9的活化。pylori可直接诱导SGC-7901细胞凋亡。SGC-7901细胞与H.幽门。H. pylori在蛋白和mRNA水平上调Bid和Bax的表达，并诱导caspase-3和-9的时间依赖性激活。Caspase-3抑制剂预孵育可明显抑制SGC-7901细胞凋亡（6、12、24和48 h时AI分别为1.72 ± 0.59%、2.97 ± 0.55%、4.38 ± 1.56%和3.29 ± 0.83%），和半胱天冬酶-9（6、12、24和48 h时AI分别为2.47 +/-0.53%、6.68 +/-0.47%、5.97 +/-0.46%和5.43 +/-0.15%）。caspase-8抑制剂也降低了H. pylori诱导的细胞凋亡率为20%。pylori感染诱导胃癌细胞凋亡及caspase-3和caspase-9的激活。此外，半胱天冬酶抑制剂显著抑制H。pylori诱导的细胞凋亡。这些结果表明，线粒体途径可能是H。幽门螺杆菌诱导的胃上皮细胞凋亡。
Background and Aims: To clarify the role of the mitochondrial pathway in apoptosis induced by H. pylori infection in gastric epithelial cells.Methods: Cells of a gastric adenocarcinoma cell line SGC-7901 were co-cultured with H. pylori NCTC 11637, with or without preincubation with the inhibitors of caspases -3, -8, and -9. Apoptosis was determined by flow cytometry. RT-PCR was used to determine the expression of Bid, Bax, and Bcl-2 mRNA, and Western blotting was used to determine the expression of Bid, Bax, and Bcl-2 proteins, and the activation of caspases -3 and -9.Results: H. pylori directly induced apoptosis in SGC-7901 cells. Apoptotic indices (AIs) were 6.30 +/- 0.40%, 11.57 +/- 0.78%, 8.63 +/- 0.67%, and 7.22 +/- 0.97%, respectively, at 6, 12, 24, and 48 h after SGC-7901 cells were co-cultured with H. pylori. H. pylori up-regulated the expression of Bid and Bax at both protein and mRNA levels, and induced a time-dependent activation of caspases -3 and -9. Apoptosis was inhibited significantly by the preincubation of SGC-7901 cells with the inhibitors of caspase-3 (AIs were 1.72 +/- 0.59%, 2.97 +/- 0.55%, 4.38 +/- 1.56%, and 3.29 +/- 0.83%, respectively, at 6, 12, 24, and 48 h), and caspase -9 (AIs were 2.47 +/- 0.53%, 6.68 +/- 0.47%, 5.97 +/- 0.46%, and 5.43 +/- 0.15%, respectively, at 6, 12, 24, and 48 h). The caspase-8 inhibitor also reduced H. pylori-induced apoptosis by 20%.Conclusions: H. pylori infection induces apoptosis and the activation of caspases -3 and -9 in gastric cancer cells. Moreover, the caspase inhibitors significantly suppress H. pylori-induced apoptosis. These findings suggest that the mitochondrial pathway may be the major pathway in H. pylori-induced apoptosis in gastric epithelial cells.