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Abstract Salmonella Typhimurium is one of the most widely studied bacteria-mediated cancer therapies. OMVs is a much safer form of Salmonella that could be effective in small doses. This study was directed towards assessing the in vitro S. Typhimurium OMVs antitumor effect, alone or combined with chemotherapeutic drugs. The cytotoxic effect of S. Typhimurium OMVs and chemotherapeutic drugs on MCF-7 and Caco-2 cell lines at different doses was expressed as cell viability. Using neutral red uptake assay revealed that S. Typhimurium OMVs were cytotoxic to cancer cell lines and decreased their viability. It was found that the IC50 value of S. Typhimurium OMVs was 16.7 og/ml on MCF-7 and 14.4 og/ml on Caco-2 cells. On the other hand, the IC50 of Paclitaxel on MCF-7 was 2.2 oM, while 5.3 oM was the IC50 of Doxorubicin on Caco-2 cells. Combining S. Typhimurium OMVs with chemotherapies exhibited a magnificent cytotoxic effect expressed by changes in the morphology and decrease in viability of MCF-7 and Caco-2 cells. These results were significantly different from untreated controls. Similar results were detected in vivo This may render S. Typhimurium OMVs as a safe promising novel antitumor monotherapy, and an adjuvant potentiating the antitumor efficiency of chemotherapies and decreasing their harmful side effects. The S. Typhimurium OMVs antitumor effect refers to its anti proliferative, antiangiogenic effect besides enhancing recruitment of NK cells to the tumore site and mediating non-inflammatory tumor cells self-destructing mechanisms such as apoptosis and autophagy |