XIAP在TRAIL抗性细胞HCT116 bax^(-/-)中的作用机制研究  

The Machnism of XIAP and TRAIL Resistance in HCT116 bax^(-/-)

作　　者：龙添珍 黄学琴[1] 刘海朋[1] 冯海燕[1] 徐阳[1] 梁朋[1] LONG Tian-Zhen HUANG Xue-Qin LIU Hai-Peng FENG Hai-Han XU Yang LIANG Peng(College of Life Sciences, Sichuan University, Chengdu 610064)

机构地区：[1]四川大学生命科学学院,成都610064

出　　处：《四川大学学报（自然科学版）》2016年第6期1398-1402,共5页Journal of Sichuan University(Natural Science Edition)

基　　金：国家自然科学基金(81171955);国家重点基础研究发展计划(202CB910702)

摘　　要：为了探索结直肠癌细胞HCT116抗TRAIL诱导凋亡的分子机制,本课题以其抗性细胞HCT116 bax^(-/-)为实验对象进行了研究.通过利用目前最热的基因定点编辑技术Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated(Cas)9系统将HCT116bax^(-/-)的XIAP(X-linked inhibitor of apoptosis protein)基因彻底敲除后,用TRAIL处理,发现其恢复了对TRAIL的敏感,形态学发生了明显凋亡,而且western blot检测显示PARP蛋白发生了完全剪切.由此证明敲除XIAP基因能克服HCT116 bax^(-/-)对TRAIL的抗性.这些发现对肿瘤细胞抗TRAIL的分子机理研究以及肿瘤的个性化治疗有非常重要的意义.To explore the mechanism of human colorectal cancer HCT116 resistant to TRAIL, the resist- ant ceils HCTll6 bax-/ which are targeted deletion of bax gene were used to study in this proiect. By using the gene-targeting technology CRISPR/Cas 9 system, the XIAP gene was knocked out completely. Then treated with TRAIL, the resistant ceils recovered the sensitive to TRIAL. It not only presented apoptosis at morphology lever, but also the PARP was cleaved completely on western blot. It showed that, the loss of XIAP led to HCTll6 bax/ ceils to overcome TRAIL resistance caused by bax dele- tion. This finding is significant for future study of the molecular mechanism behind cancer cell resistance to TRAIL and may help future personalized anti-cancer treatment.

关 键 词：TRAIL HCT116 bax-／- XIAP CRISPR／Cas9 细胞凋亡 

分 类 号：Q291[生物学—细胞生物学]