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

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.

Keywords

• breast cancer stem cells
• human telomerase reverse transcriptase
• oncolytic adenovirus
• gene therapy