期刊
ONCOTARGET
卷 7, 期 30, 页码 48027-48037出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10338
关键词
dragon; oxaliplatin resistance; colon cancer; JNK; p38 MAPK
资金
- National Natural Science Foundation of China [81570496, 81370505, 81370591, 81271895, 91229201]
- 973 programs [2015CB553800]
- Natural Science Foundation of Fujian Province of China [2013J01358]
- Ministry of Health Foundation for State Key Clinical Department in China
- key lab of GI microecology and digestive diseases in Xiamen, China
- Chinese University of Hong Kong
- RGC/GRF [CUHK477311]
- RGC-NSFC joint grant [N_CUHK432/12, 81261160507]
- Ministry of Health Foundation for State Key Clinical Departments in China
- Cross-Strait Joint Laboratory of Digestive Disease in Xiamen University
- Key Laboratory of GI Microecology and Digestive Diseases in Xiamen, China
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.
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