Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
Cancer Biother Radiopharm. 2012 Mar;27(2):164-8. doi: 10.1089/cbr.2011.1018. Epub 2011 Oct 19.
The importance of apoptosis during the process of inhibiting tumorigenesis has been recognized. The role of BH3-only proapoptotic protein Bcl-2-associated death (BAD) in tumor growth remains controversial. The aim of this study was to explore the role of BAD in lung cancer cells. Our study showed that expression of BAD was upregulated in A549 cells by a recombinant lentivirus overexpressing BAD. In vitro, BAD overexpression significantly inhibited A549 cell proliferation and induced apoptosis in cell proliferation and apoptosis assays, respectively. The effect of BAD on A549 cells was studied in tumor xenograft of nude mice and the results showed that the tumor volume in the experimental group was smaller than the control groups. Further, immunohistochemical technique was used to determine the cell proliferation and apoptosis status of the lung tumor xenograft cells. This demonstrated that the in vivo and in vitro results were consistent. Taken together, our results indicate that overexpression of BAD inhibits the growth of A549 cells in vitro and in vivo, through inhibiting cell proliferation and inducing apoptosis. Thus, BAD could be a potential therapeutic target.
细胞凋亡在抑制肿瘤发生过程中的重要性已得到认可。BH3 仅含有促凋亡蛋白 Bcl-2 相关死亡(BAD)在肿瘤生长中的作用仍存在争议。本研究旨在探讨 BAD 在肺癌细胞中的作用。我们的研究表明,重组过表达 BAD 的慢病毒可上调 A549 细胞中 BAD 的表达。在体外,BAD 过表达显著抑制 A549 细胞增殖,并分别在细胞增殖和凋亡检测中诱导凋亡。在裸鼠肿瘤异种移植中研究了 BAD 对 A549 细胞的影响,结果表明实验组的肿瘤体积小于对照组。此外,还采用免疫组织化学技术测定了肺肿瘤异种移植细胞的细胞增殖和凋亡状态。这表明体内和体外结果是一致的。综上所述,我们的结果表明,BAD 的过表达通过抑制细胞增殖和诱导凋亡,体外和体内均可抑制 A549 细胞的生长。因此,BAD 可能是一个有潜力的治疗靶点。