1. Overexpression of Smac by an Armed Vesicular Stomatitis Virus Overcomes Tumor Resistance
- Author
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Weike Li, Ravi Chakra Turaga, Xin Li, Malvika Sharma, Zahra Enadi, Sydney Nicole Dunham Tompkins, Kyle Christian Hardy, Falguni Mishra, Jun Tsao, Zhi-ren Liu, Daping Fan, and Ming Luo
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Despite reports of successful clinical cases, many tumors appear to resist infection by oncolytic viruses (OVs). To circumvent this problem, an armed vesicular stomatitis virus was constructed by inserting a transgene to express Smac/DIABLO during virus infection (VSV-S). Endogenous Smac in HeLa cells was diminished during wtVSV infection, whereas the Smac level was enhanced during VSV-S infection. Apoptosis was readily induced by VSV-S, but not wtVSV, infection. More importantly, the tumor volume was reduced to a larger extent when xenografts of 4T1 cells in BALB/c mice and OV-resistant T-47D cells in nude mice were intratumorally injected with VSV-S. VSV-S represents a novel mechanism to overcome tumor resistance, resulting in more significant tumor regression due to enhanced apoptosis.
- Published
- 2019
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