Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells

// Ying Shi 1, * , Xiao-Xiao Huang 1, * , Guo-Bin Chen 1, 6, * , Ying Wang 1 , Qiang Zhi 1 , Yuan-Sheng Liu 1 , Xiao-Ling Wu 1 , Li-Fen Wang 1 , Bing Yang 1 , Chuan-Xing Xiao 1 , Hui-Qin Xing 5 , Jian-Lin Ren 1 , Yin Xia 3, 4 , Bayasi Guleng 1, 2 1 Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China 2 State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China 3 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China 4 School of Biomedical Sciences Core Laboratory, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China 5 Department of Basic Medical Sciences, Institute of Neuroscience, Medical College of Xiamen University, Xiamen, China 6 Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China * These authors contributed equally to this work Correspondence to: Bayasi Guleng, email: bayasi@xmu.edu.cn Yin Xia, email: Xia.Yin@cuhk.edu.hk Ying Shi, email: shiying@stu.xmu.edu.cn Keywords: Dragon, oxaliplatin resistance, colon cancer, JNK, p38 MAPK Received: December 21, 2015 Accepted: June 12, 2016 Published: June 30, 2016 ABSTRACT 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.