Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells.
Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells.
复制标题
Dragon (RGMb) 诱导结肠癌细胞对奥沙利铂耐药
DOI：
10.18632/oncotarget.10338
复制
发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Guleng B
中科院分区：
文献类型：
--
作者：
Shi Y;Huang XX;Chen GB;Wang Y;Zhi Q;Liu YS;Wu XL;Wang LF;Yang B;Xiao CX;Xing HQ;Ren JL;Xia Y;Guleng B
结直肠癌是最常见的癌症之一，也是癌症死亡的主要原因。化疗耐药仍然是治疗晚期结直肠癌的主要挑战。因此，识别诱导耐药的靶点是开发克服耐药的新型药物的首要任务。Dragon(也被称为RGMb)是排斥性引导分子(RGM)家族的成员。我们之前的研究表明，在人类患者中，Dragon的表达随着结直肠癌的进展而增加。在本研究中，我们发现龙血竭在奥沙利铂存在的情况下抑制了CMT93和HCT116细胞的凋亡并提高了细胞的存活率。龙血竭诱导小鼠移植瘤对奥沙利铂耐药。龙血竭从机制上抑制了奥沙利铂诱导的JNK和p38MAPK的激活以及caspase-3和PARP的裂解。我们的结果表明，Dragon可能是诱导结直肠癌耐药的一个新靶点。
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.