肿瘤对肿瘤坏死因子相关凋亡诱导配体的耐受机制及增敏实验的研究

Progress of mechanisms for resistance and sensibility strengthening of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand

肿瘤坏死因子相关凋亡诱导配体(TRAIL)是近年来发现的凋亡分子,能选择性诱导转化细胞、肿瘤细胞和病毒感染细胞发生凋亡,而对大多数正常细胞几乎没有毒性。但如果TRAIL在肿瘤中介导的凋亡信号传递受阻或者出现其他信号传导通路的激活,就可引起肿瘤对TRAIL的耐受。如果TRAIL蛋白与化疗药物或其他方法联合应用,就可以上调DR4、DR5、caspase3、caspase8或Bax等促凋亡因子的表达,或下调Bcl-XL、cFLIP等凋亡抑制因子的表达,从而克服肿瘤细胞对TRAIL的耐受或提高对TRAIL的敏感性。本文主要概述肿瘤细胞对TRAIL的耐受机制及克服耐受、增强肿瘤细胞凋亡敏感性的实验研究进展。

Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） was found in recent years, which can selectively induce the apoptosis of transformed cells, the tumor cells, and virus-infected cell without toxicity to the majority of normal cells. But if TRAIL transduction cancer mediated-apoptosis signal is disrupted or other signal pathway transduction is activated, the cause of resistance to TRAIL mediated-apoptosis in＇cancer could be induced. TRAIL protein combining chemotherapeutics or other means may overcome the resistance to TRAIL. The synergy can be achieved either through upregulating DR4 or DR5, caspase-3, caspase-8, or Bax, etc, for promoting the expression of apoptosis factors or through down-regulating Bcl-XL or cFLIP, etc, for prohibiting the expression of apoptosis factor; leading to overcome the resistance or raisng the sensitivity of tumor cells to TRAIL. Here the mechanisms of resistance to TRAIL in cancer and the experimental progress of overcoming the resistance to TRAIL and enhancing the sensitivity of tumor cells apoptosis were introduced.