Ad-VT (Ad-Apoptin-hTERTp-E1a) is a type of oncolytic adenovirus with dual specific
tumor cell death ability. It can effectively induce cell death of
breast cancer cells and has better effect when used in combination with
chemotherapy drugs. However, it has not been reported whether Ad-VT reduces the resistance of
breast cancer cells to
chemotherapy drugs. The purpose of this study is to investigate the effect of Ad-VT on drug resistance of
Adriamycin-resistant
breast cancer cells. For this, the effects of different doses of Ad-VT on the resistance of
breast cancer cells to
Adriamycin were analyzed using qualitative and quantitative experiments in vitro and in vivo. The Ad-VT can reduce the resistance of MCF-7/ADR to
adriamycin, which is caused by the reduction of
MRP1 protein level in MCF-7/ADR cells
after treatment with Ad-VT, and
MRP1 can be interfered with by autophagy inhibitors. Subsequently, the upstream signal of autophagy was analyzed and it was found that Ad-VT reduced the resistance of cells to
doxorubicin by reducing the level of mTOR, and then the analysis of the upstream and downstream
proteins of mTOR found that Ad-VT increased the sensitivity of MCF-7/ADR cells to
adriamycin by activating AMPK-mTOR-eIF4F signaling axis. Ad-VT can not only significantly induce cell death in MCF-7/ADR cells, but also improved their sensitivity to
Adriamycin. Therefore, the combination of Ad-VT and
chemotherapy drugs may become a new strategy for the treatment of
breast cancer in overcoming
Adriamycin resistance.