期刊
MOLECULAR CANCER RESEARCH
卷 10, 期 12, 页码 1567-1579出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-12-0209-T
关键词
-
资金
- National Cancer Institute (NCI) [CA140554]
- DOD-CDMRP funds [BC103217: W81XWH-11-1-0128]
- [P30CA047904]
Colorectal cancer is the third leading cause of cancer-related mortality in the world. The main cause of death because of colorectal cancer is hepatic metastases, which can be treated using isolated hepatic perfusion (IHP), allowing treatment of colorectal metastasis with various methods. In this study, we present a novel potent multimodality strategy comprising humanized death receptor 4 (DR4) antibody mapatumumab in combination with oxaliplatin and hyperthermia to treat human colon cancer cells. Oxaliplatin and hyperthermia sensitized colon cancer cells to mapatumumab in the mitochondrial-dependent apoptotic pathway and increased reactive oxygen species (ROS) production, leading to Bcl-xL phosphorylation at serine 62 in a c-jun-NH2-kinase (JNK)-dependent manner. Overexpression of Bcl-xL reduced the efficacy of the multimodality treatment, whereas phosphorylation of Bcl-xL decreased its antiapoptotic activity. The multimodality treatment dissociated Bcl-xL from Bax, allowing Bax oligomerization to induce cytochrome c release from mitochondria. In addition, the multimodality treatment significantly inhibited colorectal cancer xenografts' tumor growth. The successful outcome of this study will support the application of multimodality strategy to colorectal hepatic metastases. Mol Cancer Res; 10(12); 1567-79. (C) 2012 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据