Recombinant Oncolytic Adenovirus Combined with Cyclophosphamide Induces Synergy in the Treatment of Breast Cancer in vitro and in vivo

文献类型： 外文期刊

第一作者： Wang, Jing

作者： Wang, Jing;Zuo, Shuting;Zhang, Yan;Shi, Ying;Du, Tonghua;Li, Shanzhi;Han, Jicheng;Jin, Ningyi;Li, Yiquan;Li, Xiao;Jin, Ningyi;Li, Xiao;Jin, Ningyi;Li, Yiquan;Li, Xiao

作者机构：

关键词： cyclophosphamide; recombinant adenovirus; breast cancer; synergy; toxicity

期刊名称：CANCER MANAGEMENT AND RESEARCH （ 影响因子：3.602； 五年影响因子：3.811 ）

ISSN： 1179-1322

年卷期： 2022 年 14 卷

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收录情况： SCI

摘要： Purpose: Oncolytic virus therapy has gradually become an integral approach in cancer treatment. We explored the therapeutic effects of the combination of a dual cancer-selective anti-tumor recombinant adenovirus (Ad-Apoptin-hTERTp-E1a) and cyclophosphamide on breast cancer cells.Methods: The inhibition of MCF-7 and MDA-MB-231 breast cancer cells by Ad-Apoptin-hTERTp-E1a (Ad-VT), cyclophosphamide, and Ad-VT + Cyclophosphamide was investigated using the CCK-8 assay. The combination index (CI) was calculated using CalcuSyn software to determine the best combination based on the inhibition rates of the different treatment combinations. The CCK-8 assay and crystal violet staining were used to detect the cytotoxicity of the combined Ad-VT and cyclophosphamide in breast cancer cells and breast epithelial cells. Subsequently, Hoechst staining, annexin V flow cytometry, and JC-1 staining were used to analyze the inhibitory pathway of Ad-VT plus cyclophosphamide on breast cancer cells. Cell migration and invasion of breast cancer cells were assessed using the cell-scratch and Transwell assays. The anti-tumor effects of different treatment groups in a tumor-bearing nude mouse model also were analyzed. Results: The treatment combination of Ad-VT (40 MOI) and cyclophosphamide (400 mu M) significantly inhibited MCF-7 and MDA-MB-231 cells and reduced the toxicity of cyclophosphamide in normal cells. Ad-VT primarily induced breast cancer cell apoptosis through the endogenous apoptotic pathway. Apoptosis was significantly increased after treatment with Ad-VT plus cyclophosphamide. The combination significantly inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells. The in vivo experiments demonstrated that exposure to Ad-VT plus cyclophosphamide significantly inhibited tumor growth and extended the survival time of the nude mice.Conclusion: Ad-VT plus cyclophosphamide reduced toxicity and exhibited increased efficacy in treating breast cancer cells.

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