Vaccinia Virus-Mediated IL-24 Gene Expression Inhibits the Growth of Human Breast Cancer by Inducing Apoptosis

Abstract

Breast cancer is one of the most leading causes of cancer-related death in the world. Short survival, recurrent disease, chemotherapy-resistant and highly aggressive clinical course make it looking forward to novel targeted therapeutic strategies. Oncolytic vaccinia virus is an attractive candidate for cancer therapy due to its tumor cell-specific replication causing lysis of infected tumor cells as well as a delivery vector to overexpress therapeutic transgenes. Interleukin-24 (IL-24) is a novel tumor suppressor cytokine that selectively induces apoptosis in a wide variety of tumor types, including breast cancer. In present study, a targeted oncolytic vaccinia virus armed with IL-24 gene (VG9-IL-24) was constructed to evaluate its antitumor effects both in vitro and in vivo. We observed VG9-IL-24 efficiently infected and selectively eradicated breast cancer cells with no significant cytotoxicity to normal cells. VG9-IL-24 induced increased number of apoptotic cells and blocked breast cancer cells in the G2/M phase of the cell cycle. Western blotting results indicated that VG9-IL-24-mediated apoptosis was related to PI3K/β-catenin signaling pathway. In MDA-MB-231 xenograft mouse model, VG9-IL-24 delayed tumor growth and improved survival. Our findings provided documentation that VG9-IL-24 may be an innovative therapy for breast cancer with tumor-specific lysing and apoptosis-inducing. Funding: This work was supported by grants from the National Natural Science Foundation of China (81703061). The funding source was used for data collection and analysis. Declaration of Interest: None. Ethical Approval: The animal experiment was approved by the Institutional Animal Care and Use Committees (IACUC) of Jiangsu Institute of Nuclear Medicine (JSINM2010007).