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The limited selectivity of therapeutic agents for tumor cells and their inability to act on poorly vascularized areas of tumors, remain among the primary limitations to cancer therapy. Several studies reported that Salmonella typhimurium VNP20009 (VNP) preferentially targets hypoxic/anoxic cores of solid tumors. Here the authors compare the antitumor effect of VNP with doxorubicin (Dox) and a combination of both agents, in a murine model of Ehrlich ascites carcinoma (EAC). Methods: Mice were randomly divided into four control groups and three treatment groups receiving VNP, Dox, or a combination of both. Plasma levels of the liver enzymes ALT and AST, and levels of urea and creatinine were measured colorimetrically; vascular endothelial growth factor (VEGF) was measured using ELISA and total free radicals were measured using electron spin resonance (ESR). Histopathological studies were performed on liver and tumor tissues. Apoptosis/necrosis and the tumor suppressor protein p53 levels were assayed by immunohistochemistry. Results: VNP treatment resulted in normal levels of ALT, AST, urea and creatinine. Less dense tumor cells with regeneration of skeletal muscle and almost normal architecture of liver tissues were observed in animals receiving VNP and combined therapy. Tumor volumes and VEGF levels were significantly lower in these two groups. Free radicals significantly increased in Dox-receiving group compared to the VNP and the combination group. Late stage apoptotic/necrotic cells were observed in tumor tissues treated with VNP, Dox or their combination, and p53 levels were higher in the same groups. Conclusion: Monotherapy with VNP showed comparable antitumor effects to Dox, but seems to obviate the reported negative side-effects of Dox.

advances in cancer: research and treatment

Regression of Murine Ehrlich Ascites Carcinoma Using Tumor-Targeting Salmonella VNP20009 - Comparison with the Effect of the Anticancer Drug Doxorubicin