诱导程序性坏死以规避肿瘤细胞耐药的研究进展

Circumventing drug resistance of tumor cells by induction of necroptosis

程序性坏死是一种不依赖含半胱氨酸的天冬氨酸蛋白水解酶的可调控程序性细胞死亡途径,具有与坏死相同的形态学特征及与凋亡相似的分子生物学特点。目前临床化疗的主要障碍是肿瘤耐药,它与细胞表面药泵蛋白高表达介导的多药耐药及细胞凋亡通路被阻断有关。因此,诱导肿瘤细胞发生程序性坏死可能成为逆转多种肿瘤耐药的强有力武器。本文主要从程序性坏死、肿瘤细胞耐药机制及诱导程序性坏死逆转肿瘤细胞耐药的相关研究共三个方面进行综述。

Necroptosis is a caspase-independent, regulable programmed cell death pathway, which possesses the same mor-phological characteristics of necrosis and similar molecular biological characteristics with apoptosis. Currently, the main obstacle in chemotherapy is drug resistance of tumor cells, mainly due to multidrug resistance mediated by high expression of ATP-dependent drug transporters and the blockade of apoptosis pathway. Thus, the induction of necroptosis may act as a potentially powerful weapon to re-verse a variety of tumor resistance. This review includes three parts：necroptosis, its relation with apoptosis and autophagy, drug resist-ance mechanism of tumor cells and recent advances in the induction of necroptosis.