title: Enhanced therapeutic effect by combination of tumor-targeting Salmonella and endostatin in murine melanoma model.
abstract: The growth of tumor is angiogenesis-dependent and it often contains hypoxia and necrotic areas. Salmonella VNP20009 could target and replicate in hypoxia and necrotic areas within tumor and induce antitumor effect. Angiogenesis inhibitor endostatin could reduce tumor angiogenesis and inhibit its growth. However, in the phase I trials of VNP20009 and endostatin at the maximum-tolerated dose, no antitumor effects for bacteria therapy and minor therapeutic effects for endostatin treatment were seen. The ineffectiveness of these agents in clinical trials suggests that the combination of these agents with synergic modalities might be necessary. Here we described antitumor effects mediated by the combination of VNP20009 with recombinant human endostatin in B16F10 murine melanoma model with the aim to exploit tumor-targeting of bacteria and anti-angiogenesis strategy to enhance therapeutic efficacy. Combination therapy of these agents significantly enhanced antitumor effects by inducing greater tumor growth inhibition, more severe tumor tissue necrosis as well as less blood vessel density than those induced by either of treatments. The findings suggest that the combination of tumor-targeting bacteria with angiogenesis inhibitor might be of value for the treatment of solid tumors.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and Department of Biochemistry, College of Life Sciences, Nanjing University, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Jia
authors.forename: Han-Mei
authors.initials: HM
authors.lastname: Xu
authors.forename: Ding-Yuan
authors.initials: DY
authors.lastname: Ma
authors.forename: Qin-Gang
authors.initials: QG
authors.lastname: Hu
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Huang
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Jiang
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Li
authors.forename: Kun-Zhi
authors.initials: KZ
authors.lastname: Jia
authors.forename: Qi-Lai
authors.initials: QL
authors.lastname: Huang
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001428:Bacterial Vaccines; D003131:Combined Modality Therapy; D043169:Endostatins / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000737:chemistry / Q000188:drug therapy*; D051379:Mice; D014613:Vaccines, Attenuated / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D020533:Angiogenesis Inhibitors; D001428:Bacterial Vaccines; D043169:Endostatins; C465023:VNP 20009; D014613:Vaccines, Attenuated; D042461:Vascular Endothelial Growth Factor A