J Cancer 2020; 11(5):1017-1026. doi:10.7150/jca.37590 This issue
1. NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
2. Wuxi Children's Hospital, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, China.
3. School of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Background: Breast cancer is a heterogeneous disease with high aggression and novel targeted therapeutic strategies are required. Oncolytic vaccinia virus is an attractive candidate for cancer treatment due to its tumor cell-specific replication causing lysis of 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 this study, we used vaccinia virus as a delivery vector to express IL-24 gene and antitumor effects were evaluated both in vitro and in vivo. Methods: The vaccinia virus strain Guang9 armed with IL-24 gene (VG9-IL-24) was constructed via disruption of the viral thymidine kinase (TK) gene region. The cytotoxicity of VG9-IL-24 in various breast cancer cell lines was assessed by MTT and cell cycle progression and apoptosis were examined by flow cytometry. In vivo antitumor effects were further observed in MDA-MB-231 xenograft mouse model. Results: In vitro, VG9-IL-24 efficiently infected and selectively killed breast cancer cells with no strong 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 vivo, VG9-IL-24 delayed tumor growth and improved survival. Conclusions: Our findings provided documentation that VG9-IL-24 was targeted in vitro and exhibited enhanced antitumor effects, and it may be an innovative therapy for breast cancer.
Keywords: oncolytic vaccinia virus, interleukin-24, breast cancer, gene therapy, apoptosis.