Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells
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Ying Shi1,*, Xiao-Xiao Huang1,*, Guo-Bin Chen1,6,*, Ying Wang1, Qiang Zhi1, Yuan-Sheng Liu1, Xiao-Ling Wu1, Li-Fen Wang1, Bing Yang1, Chuan-Xing Xiao1, Hui-Qin Xing5, Jian-Lin Ren1, Yin Xia3,4, Bayasi Guleng1,2
1Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
2State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China
3School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
4School of Biomedical Sciences Core Laboratory, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China
5Department of Basic Medical Sciences, Institute of Neuroscience, Medical College of Xiamen University, Xiamen, China
6Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China
*These authors contributed equally to this work
Bayasi Guleng, email: [email protected]
Yin Xia, email: [email protected]
Ying Shi, email: [email protected]
Keywords: Dragon, oxaliplatin resistance, colon cancer, JNK, p38 MAPK
Received: December 21, 2015 Accepted: June 12, 2016 Published: June 30, 2016
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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