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Salmonella inhibit tumor angiogenesis by downregulation of vascular endothelial growth factor via hypoxic-induced factor-1α

Date

19 Dec 2015

Session

Poster presentation 1

Presenters

Che-Hsin Lee

Citation

Annals of Oncology (2015) 26 (suppl_9): 1-7. 10.1093/annonc/mdv517

Authors

C. Lee

Author affiliations

  • Department Of Microbiology, China Medical University, 40402 - Taichung/TW
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Resources

Aim/Background

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.

Methods

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.

Results

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.

Conclusions

These results suggest that the Salmonella therapy, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.

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