Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):272-6. doi: 10.1016/j.bbrc.2009.11.048. Epub 2009 Nov 12.
Antibodies against the COOH-terminal domain of cell surface GRP78 induce apoptosis in cancer cell lines via activation of p53 signaling. We now have studied the effects of PFT-alpha, an inhibitor of p53-mediated apoptotic pathways, on anti-GRP78 antibody-induced activation of p53 and pro-apoptotic signaling in 1-LN prostate cancer cells. Pretreatment of 1-LN cancer cells with this agent significantly inhibited antibody or doxorubicin-induced upregulation of p53. Concomitantly, PFT-alpha treatment prevented down regulation of ERK1/2 activation by either antibody or doxorubicin. Likewise, PFT-alpha prevented increases in the pro-apoptotic proteins BAD, BAK, BAX, PUMA, and NOXA as well as activation of caspases-3, -7, and -9. We conclude that antibody-induced apoptosis in prostate cancer cells is mediated predominantly by p53 using the mitochondrial pathway of apoptosis.
针对细胞表面 GRP78 的 COOH 末端域的抗体通过激活 p53 信号诱导癌细胞系凋亡。我们现在已经研究了 PFT-α（一种抑制 p53 介导的凋亡途径的抑制剂）对抗 GRP78 抗体诱导的 p53 和促凋亡信号在 1-LN 前列腺癌细胞中的作用。该试剂预处理 1-LN 癌细胞可显著抑制抗体或阿霉素诱导的 p53 上调。同时，PFT-α 处理可防止抗体或阿霉素诱导的 ERK1/2 激活下调。同样，PFT-α 可防止促凋亡蛋白 BAD、BAK、BAX、PUMA 和 NOXA 的增加以及 caspase-3、-7 和 -9 的激活。我们得出结论，抗体诱导的前列腺癌细胞凋亡主要通过 p53 介导，使用线粒体凋亡途径。
