携带人端粒酶反转录酶启动子的溶瘤腺病毒RCA-TERT-Ad35对乳腺癌干细胞的靶向作用  

Oncolytic Adenovirus RCA-TERT-Ad35 Carrying Human Telomerase Reverse Transcriptase Promoter Targets Breast Cancer Stem Cells

作　　者：王炜川 陈璐璐 权香兰 李颖 金永民 金文彪 于可心 张松男 WANG Weichuan;CHEN Lulu;QUAN Xianglan;LI Ying;JIN Yongmin;JIN Wenbiao;YU Kexin;ZHANG Songnan(Department of Oncology,The Affiliated Hospital of Yanbian University,Yanji 133000,China;Postdoctoral Workstation,The Affiliated Hospital of Yanbian University,Yanji 133000,China)

机构地区：[1]延边大学附属医院肿瘤科,延吉133000 [2]延边大学附属医院博士后科研工作站,延吉133000

出　　处：《肿瘤防治研究》2019年第11期971-976,共6页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金（81560478）;吉林省科技发展计划项目-青年科研基金（20150520048JH）

摘　　要：目的探讨携带人端粒酶反转录酶启动子的溶瘤腺病毒RCA-TERT-Ad35在靶向乳腺癌干细胞中的作用。方法乳腺癌细胞系MCF-7以球体形式在加入生长因子的无血清培养基中生长。同时构建携带TERT启动子的溶瘤腺病毒RCA-TERT-Ad35,并通过溶瘤、MTT及体内抗肿瘤实验观察RCA-TERT-Ad35对干细胞样癌细胞的杀伤效果。结果与亲代细胞相比,MCF-7球体细胞显示出干细胞特性,且MCF-7球体细胞中hTERT基因过表达,其对细胞毒性剂紫杉醇具有耐药性。溶瘤腺病毒RCA-TERT-Ad35在TERT过表达的细胞中进行复制并抑制细胞生长。在裸鼠移植瘤模型中,与RCA-Ad35相比,RCA-TERT-Ad35显著抑制肿瘤生长并改善小鼠的存活状态。结论溶瘤腺病毒RCA-TERT-Ad35可优先杀伤TERT过表达的乳腺癌干细胞。Objective To investigate the role of oncolytic adenovirus RCA-TERT-Ad35 carrying human telomerase reverse transcriptase promoter in targeting breast cancer stem cells.Methods Breast cancer cell line MCF-7 propagated as spheroid bodies in growth factors-defined serum-free medium.At the same time,we constructed oncolytic adenovirus RCA-TERT-Ad35 carrying TERT promoter,and observed its killing effect on stem like-cancer cells by oncolytic assay,MTT assay and in vivo antitumor assay.Results MCF-7 sphere cells displayed CSC properties,including chemo-resistance to paclitaxel and TERT gene overexpression,compared with parental cells.Oncolytic adenovirus RCA-TERT-Ad35 replicated in TERT positive cells and inhibited cell growth.In the xenograft models,RCA-TERT-Ad35 significantly inhibited tumour growth and improved survival status of mice,compared with RCA-Ad35.Conclusion Oncolytic adenovirus RCATERT-Ad35 could kill breast cancer stem cells with TERT overexpressing preferentially.

关 键 词：乳腺癌干细胞 人端粒酶反转录酶 溶瘤腺病毒 基因治疗 

分 类 号：R737.9[医药卫生—肿瘤] R730.5[医药卫生—临床医学]