Shi Ying, Huang Xiao-Xiao, Chen Guo-Bin, Wang Ying, Zhi Qiang, Liu Yuan-Sheng, Wu Xiao-Ling, Wang Li-Fen, Yang Bing, Xiao Chuan-Xing, Xing Hui-Qin, Ren Jian-Lin, Xia Yin, Guleng Bayasi
Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.
Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.
Oncotarget. 2016 Jul 26;7(30):48027-48037. doi: 10.18632/oncotarget.10338.
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.
结直肠癌（CRC）是最常被诊断出的癌症之一，也是癌症死亡的主要原因。化疗耐药性仍然是治疗晚期CRC的主要挑战。因此，鉴定诱导耐药性的靶点是开发克服耐药性的新型药物的首要任务。Dragon（也称为RGMb）是排斥导向分子（RGM）家族的成员。我们之前表明，在人类患者中，Dragon的表达随着CRC进展而增加。在本研究中，我们发现，在存在奥沙利铂的情况下，Dragon抑制CMT93和HCT116细胞的凋亡并提高其活力。Dragon诱导异种移植肿瘤对小鼠奥沙利铂治疗产生耐药性。从机制上讲，Dragon抑制奥沙利铂诱导的JNK和p38 MAPK激活以及caspase-3和PARP裂解。我们的结果表明，Dragon可能是诱导CRC耐药性的新靶点。
