Yang Hai-Bo, Song Wei, Cheng Mei-Die, Fan Hai-Fang, Gu Xu, Qiao Ying, Lu Xin, Yu Rui-He, Chen Lan-Ying
Department of Biological Science, School of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan, Henan 467044, P.R. China.
Mol Med Rep. 2015 Apr;11(4):2749-54. doi: 10.3892/mmr.2014.3004. Epub 2014 Nov 26.
The aim of the present study was to investigate the effects of deoxycholic acid (DCA) on BGC‑823 human gastric carcinoma cells and to explore the possible mechanisms underlying any such effects. Cell proliferation was detected using a 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyl tetrazolium bromide assay, cell morphology was observed by inverted microscopy, and cell cycle progression and the mitochondrial membrane potential were analyzed using flow cytometry. The expression of Bcl‑2, Bax, p53, Cyclin D1 and cyclin‑dependent kinase (CDK)2 proteins in BGC‑823 cells was analyzed with western blotting. The results demonstrated that DCA significantly inhibited cell growth, and that the cell cycle was arrested at the G1 phase. DCA was also shown to induce BGC‑823 cell apoptosis, which was associated with the collapse of the mitochondrial membrane potential. The mitochondria‑dependent pathway was activated via an increase in the ratio of Bax:Bcl‑2 in BGC‑823 cells. In addition, the expression of p53, cyclin D1 and CDK2 was altered following DCA treatment. These results suggest that DCA induces apoptosis in gastric carcinoma cells through activation of an intrinsic mitochondrial‑dependent pathway, in which p53 is involved.
本研究的目的是探讨脱氧胆酸（DCA）对BGC-823人胃癌细胞的影响，并探究其潜在作用机制。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法检测细胞增殖，通过倒置显微镜观察细胞形态，利用流式细胞术分析细胞周期进程和线粒体膜电位。采用蛋白质印迹法分析BGC-823细胞中Bcl-2、Bax、p53、细胞周期蛋白D1和细胞周期蛋白依赖性激酶（CDK）2蛋白的表达。结果表明，DCA显著抑制细胞生长，使细胞周期停滞于G1期。DCA还可诱导BGC-823细胞凋亡，这与线粒体膜电位的崩溃有关。通过增加BGC-823细胞中Bax:Bcl-2的比例激活线粒体依赖性途径。此外，DCA处理后p53、细胞周期蛋白D1和CDK2的表达发生改变。这些结果表明，DCA通过激活p53参与的内在线粒体依赖性途径诱导胃癌细胞凋亡。
