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

王炜川; 陈璐璐; 权香兰; 李颖; 金永民; 金文彪; 于可心; 张松男

doi:10.3971/j.issn.1000-8578.2019.18.1987

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

摘要

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。

Abstract:
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 RCA-TERT-Ad35 could kill breast cancer stem cells with TERT overexpressing preferentially.

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