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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。
Tumor necrosis factor-related apoptosis inducing li-gand (TRAIL) is the only endogenous cytokine that can induce apoptosis of cancer cells without obvious damage to the normal tissues of the body and is therefore considered as A promising anti-cancer drug. However, the current study found that many malignant tumor cells are resistant to TRAIL, leaving TRAIL a bottleneck in clinical application. There is growing evidence that some of the key signaling pathways may be involved in TRAIL resistance and that the use of targeted gene therapy strategies and the ability to partially restore cancer cell sensitivity to TRAIL with certain natural drugs or small molecule inhibitors. This article describes the mechanisms of tumor cell resistance to TRAIL and briefly summarizes strategies for how to effectively overcome and reverse TRAIL resistance.