Successful cancer therapy relies on the development of anticancer agents that can selectively and effectively deliver to tumor sites. Salmonella are Gram-negative, facultative anaerobes that are a common cause of host intestinal infections. Salmonella grow under aerobic and anaerobic conditions and they have been proven the capable of inhibiting tumor growth. However, the molecular mechanism that by which Salmonella inhibit tumor growth is still unclear. Angiogenesis plays an important role in the development and progression of tumors. We investigated the antitumor effect of Salmonella in a syngeneic murine tumor model.
Hypoxia-inducible factor-1 (HIF-1) α plays a significant role in tumor angiogenesis. We examined the molecular mechanism by which Salmonella regulate HIF-1α-dependent expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor.
Herein, the expression of VEGF was decreased by treatment with Salmonella in tumor cells .The conditioned medium from Salmonella -treated cells inhibited the proliferation of endothelial cells. Salmonella inhibited the expression of HIF-1α, as well as downregulated its upstream signal mediator protein kinase B (AKT). Salmonella significantly inhibited the tumor growth in vivo and immunohistochemical studies in the tumors revealed decreased intratumoral microvessel density.
These results suggest that the Salmonella therapy, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors.
Clinical trial identification
All authors have declared no conflicts of interest.