Li Yaru, Zhu Yilong, Han Jicheng, Fang Jinbo, Xiu Zhiru, Li Shanzhi, Li Wenjie, Yang Xia, Jin Ningyi, Sun Lili, Li Xiao, Li Yiquan
Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China.
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
Front Mol Biosci. 2021 Nov 19;8:763500. doi: 10.3389/fmolb.2021.763500. eCollection 2021.
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 and . 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.
腺病毒载体VT（Ad-Apoptin-hTERTp-E1a）是一种具有双重特异性肿瘤细胞死亡能力的溶瘤腺病毒。它能有效诱导乳腺癌细胞死亡，与化疗药物联合使用时效果更佳。然而，Ad-VT是否能降低乳腺癌细胞对化疗药物的耐药性尚未见报道。本研究旨在探讨Ad-VT对阿霉素耐药乳腺癌细胞耐药性的影响。为此，通过定性和定量实验分析了不同剂量的Ad-VT对乳腺癌细胞对阿霉素耐药性的影响。Ad-VT可降低MCF-7/ADR对阿霉素的耐药性，这是由于Ad-VT处理后MCF-7/ADR细胞中MRP1蛋白水平降低所致，且自噬抑制剂可干扰MRP1。随后，对自噬的上游信号进行分析，发现Ad-VT通过降低mTOR水平降低细胞对阿霉素的耐药性，然后对mTOR的上下游蛋白进行分析，发现Ad-VT通过激活AMPK-mTOR-eIF4F信号轴提高MCF-7/ADR细胞对阿霉素的敏感性。Ad-VT不仅能显著诱导MCF-7/ADR细胞死亡，还能提高其对阿霉素的敏感性。因此，Ad-VT与化疗药物联合使用可能成为克服阿霉素耐药性治疗乳腺癌的新策略。
