BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer.
BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer.
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BAD 过表达通过线粒体依赖性途径抑制非小细胞肺癌细胞生长并诱导细胞凋亡
DOI：
10.1186/1475-2867-13-53
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发表时间：
2013-06-01
影响因子：
5.8
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Jiang L;Luo M;Liu D;Chen B;Zhang W;Mai L;Zeng J;Huang N;Huang Y;Mo X;Li W
促凋亡的Bcl - 2蛋白BAD在人类细胞中启动凋亡，并已被确定为非小细胞肺癌（NSCLC）的一个预后标志物。在本研究中，我们旨在探索BAD在非小细胞肺癌中的功能。
通过用野生型BAD转染不同的非小细胞肺癌细胞系来实现BAD的过表达。在体外对细胞增殖、细胞周期、凋亡和侵袭进行了表征。在体内分析了致瘤性。进行蛋白质印迹法以确定BAD过表达对Bcl - 2家族蛋白和凋亡相关蛋白的影响。
在体外，BAD过表达显著抑制H1299、H292和SPC - A1细胞的增殖，但对SK - MES - 1和H460细胞系无此作用。BAD过表达在体内也降低了H1299/SPC - A1细胞的致瘤性。然而，在所有这些细胞系中未观察到对细胞周期分布和侵袭有明显影响。BAD过表达在所有细胞类型中也诱导凋亡，在此过程中线粒体细胞色素c（cyto - c）和半胱天冬酶3的表达增加，而Bcl - xl、Bcl - 2、Bax和半胱天冬酶8的表达未改变。这些发现表明，一个线粒体途径参与了BAD过表达介导的凋亡，在此过程中细胞色素c从线粒体释放以激活半胱天冬酶3。
我们的数据表明，BAD表达增加可增强凋亡，并对非小细胞肺癌中的细胞增殖和肿瘤生长有负面影响。BAD是肿瘤干预的一个新的潜在靶点。
BackgroundThe pro-apoptotic Bcl-2 protein BAD initiated apoptosis in human cells and has been identified as a prognostic marker in non-small cell lung cancer (NSCLC). In this study, we aimed to explore the functions of BAD in NSCLC.MethodsOverexpression of BAD was performed by transfecting different NSCLC cell lines with wild-type BAD. Cell proliferation, cell cycle, apoptosis, and invasion were characterizedin vitro. Tumorigenicity was analyzedin vivo. Western blot was performed to determine the effects of BAD overexpression on the Bcl-2 family proteins and apoptosis-related proteins.ResultsOverexpression of BAD significantly inhibited cell proliferation in H1299, H292, and SPC-A1 but not in SK-MES-1 and H460 cell linesin vitro. BAD overexpression also reduced the tumorigenicity of H1299/SPC-A1 cellin vivo. However, no appreciable effects on cell cycle distribution and invasion were observed in all these cell lines. BAD overexpression also induced apoptosis in all cell types, in which process expression of mitochondrial cytochrom c (cyto-c) and caspase 3 were increased, whereas Bcl-xl, Bcl-2, Bax and caspase 8 expressions did not changed. These findings indicated that a mitochondrial pathway, in which process cyto-c was released from mitochondrial to activate caspase 3, was involved in BAD overexpression-mediated apoptosis.ConclusionsOur data suggested that increased expression of BAD enhance apoptosis and has negative influence on cell proliferation and tumor growth in NSCLC. Bad is a new potential target for tumor interventions.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
3.7
作者：
Smith AJ;Karpova Y;D'Agostino R Jr;Willingham M;Kulik G
通讯作者：
Kulik G
影响因子：
6.2
作者：
Liu, Dan;Huang, Yi;Li, Weimin
通讯作者：
Li, Weimin
影响因子：
11.2
作者：
Lee, Keun-Wook;Kim, Sang Gyun;Bang, Yung-Jue
通讯作者：
Bang, Yung-Jue
影响因子：
8.4
作者：
Al-Bazz, Yousif O.;Underwood, James C. E.;Dobson, Pauline R. M.
通讯作者：
Dobson, Pauline R. M.