TRAIL诱导肿瘤细胞凋亡机制的研究进展.PDF

中国农学通报 2012,28(11):47-50 Chinese Agricultural Science Bulletin TRAIL诱导肿瘤细胞凋亡机制的研究进展 高 静，金天明 （天津农学院动物科学系，天津300384） 摘 要：TRAIL 具有选择性杀伤肿瘤细胞而对大多数正常细胞没有明显毒性，可通过TRAIL 胞外及胞内 凋亡通路发挥诱导肿瘤细胞凋亡作用，而正常细胞则通过NF-κB 介导、诱骗受体及c-FLIP 调节来逃逸 TRAIL 诱导的凋亡。TRAIL 与基因治疗、抗死亡受体的单克隆抗体、化疗、放疗药物及蛋白酶体抑制因 子的联合使用能明显提高肿瘤治疗的敏感性，同时还可以逆转肿瘤细胞对TRAIL 的耐药现象。因此 TRAIL 作为新一代抗肿瘤药物有望应用于临床治疗。 关键词：TRAIL ；细胞凋亡；肿瘤；治疗 中图分类号：S857.4 文献标志码：A 论文编号：2011-3970 ProgressonMechanismofApoptosisTumorCellsInducedbyTRAIL Gao Jing, Jin Tianming (DepartmentofAnimalScience,TianjinAgriculturalUniversity, Tianjin 300384) Abstract: TRAIL could selectively induced the apoptosis of tumor cells, but not the bulk normal had clear toxicity. TRAIL could induced tumor cells to apoptosis through extracellular and intracellular apoptotic pathway, however normal cells could escaped induction of TRAIL through NF-κB mediated, decoying receptors and regulation of c-FLIP. The therapeutic alliance between TRAIL and gene therapy, monoclonal antibody against death receptor, chemotherapy, radiotherapy drugs and proteasome inhibitor could elevated the sensitivity of oncotherapy, meanwhile could reversed the phenomenon of resistance of tumor cells to TRAIL. Therefore, TRAIL might became a new generation antitumor drug to clinical treatment. Keywords:TRAIL; cell apoptosis; tumor; therapy 0 引言 疗、药物蛋白酶体抑制因子等相结合使用，可增加 肿瘤坏死因子相关凋亡诱导配体(TNF related TRAIL 对肿瘤细胞的敏感度，进而协同提高了对肿瘤 [1] apoptosis inducing ligand, TRAIL) 是Wiley 等 首次从 细胞的疗效，因此，TRAIL 的联合应用有望成为为肿 人心肌cDNA 文库中克隆出来，其氨基酸顺序具有 瘤治疗的研究热点。本研究就其结构、凋亡机制及抗 T