Salmonella inhibits tumor angiogenesis by downregulation of vascular endothelial growth factor

// Dom-Gene Tu 1,2,3 , Wen-Wei Chang 4,5 , Song-Tao Lin 6 , Chun-Yu Kuo 7 , Yu-Tzu Tsao 8 and Che-Hsin Lee 6,7,9 1 Department of Nuclear Medicine, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chia-Yi, Taiwan 2 Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan 3 College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan 4 Department of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung, Taiwan 5 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan 6 Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan 7 Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan 8 Department of Medicine, Taoyuan General Hospital, Taoyuan, Taiwan 9 Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan Correspondence to: Che-Hsin Lee, email: // Keywords : Salmonella, tumor-targeting, angiogenesis, hypoxia-inducible factor-1α, vascular endothelial growth factor Received : August 10, 2015 Accepted : January 19, 2016 Published : January 27, 2016 Abstract Salmonella is a Gram-negative, facultative anaerobe that is a common cause of host intestinal infections. Salmonella grows under aerobic and anaerobic conditions, and it has been proven capable of inhibiting tumor growth. However, the molecular mechanism by which Salmonella inhibits 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 regulated vascular endothelial growth factor (VEGF), which is an important angiogenic factor. The expression of VEGF in tumor cells was decreased by treatment with Salmonella . 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 tumor growth in vivo , and immunohistochemical studies of the tumors revealed decreased intratumoral microvessel density. These results suggest that Salmonella therapy, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors.