TRAIL耐药产生的机制及逆转耐药的最新策略

The Mechanisms of TRAIL Resistance and the Novel Strategies for Reversing TRAIL Resistance

肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis inducing li-gand,TRAIL)是唯一能诱导癌细胞凋亡而对机体正常组织无明显损伤的内源性细胞因子,因而被认为是一种极具前景的抗癌药物。然而目前研究发现,许多恶性肿瘤细胞对TRAIL具有耐药性,使TRAIL在临床应用中遭遇瓶颈。越来越多的证据表明,一些关键信号通路可能与TRAIL耐药有关,且利用靶向基因治疗策略以及借助某些天然药物或小分子抑制剂能够部分恢复癌细胞对TRAIL的敏感性。该文主要描述了肿瘤细胞对TRAIL的耐药机制,并对如何有效克服和逆转TRAIL耐药的策略作了简要概括。

TNF-related apoptosis-inducing ligand （TRAIL） is an endogenous factor that can selectively induce tumor cell apoptosis without side effects to normal cells. Thus it is considered as a promising anti-cancer agent. However, present studies show that many human cancer cells are resistant to TRAIL, resulting in the arising bottleneck during the course of TRAIL clinical treatment. More and more evidence suggests that several key signal-ing pathway may be responsible for the development of resistance to TRAIL. Yet, it was reported that some natural medicines and small molecular inhibitors can partially restore the sensitive to TRAIL-induced apoptosis in cancer cells. This review mainly describes the molecular mechanisms of TRAIL resistance to tumor cells, and the underly-ing strategies for how to overcome efficiently TRAIL resistance to tumor cells.