Vesicular stomatitis virus is a potent agent for the treatment of malignant ascites

Zhou,Yi; Wen,Feng; Zhang,Pengfei; Tang,Ruilei; Li,Qiu

doi:10.3892/or.2015.4522

Vesicular stomatitis virus is a potent agent for the treatment of malignant ascites

Authors:
- Yi Zhou
- Feng Wen
- Pengfei Zhang
- Ruilei Tang
- Qiu Li
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Affiliations: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: December 24, 2015 https://doi.org/10.3892/or.2015.4522
Pages: 1573-1581

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Abstract

Cancer cells in ascites are usually exposed to a hypoxia tumor microenvironment and utilize enhanced glycolysis which produces energy and metabolizes nutrients to support proliferation. Vesicular stomatitis virus (VSV) is an oncolytic virus that relies on the host cellular metabolism for replication. We tested the efficacy of VSV on peritoneal carcinomatosis and assessed VSV replication in cancer cells from ascites. BALB/c female mice bearing peritoneal H22 or MethA cells received an i.p. administration of 1x108 PFU VSV or 1x108 PFU equivalent of UV-inactivated VSV on day 10, 12 and 14 after incubation. Administration of VSV resulted in a significant inhibition of ascites formation and prolonged survival of the treated mice. The replication of VSV was obviously enhanced in the cancer cells from the ascites. Considering the central carbon metabolic pathways, cancer cells in the malignant ascites provided more exogenous glucose, glutamine and pyruvate after VSV infection due to its unregulated glycolytic activity and glutamine metabolism. Pharmacologically, inhibition of the glycolytic pathway and glutamine metabolism reduced VSV replication, and this inhibited replication was rescued by the addition of multiple tricarboxylic acid (TCA) cycle intermediates. Our results demonstrated that metabolic adaptive processes in peritoneal carcinoma, such as high glycolytic activity and glutamine metabolism, favor VSV replication. These results suggest the clinical potency of VSV in the treatment of malignant ascites and provide new insights into the further exploration of the potential application of VSV in the treatment of hypoxia ascites cancer cells.

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