Augmented antitumor effects of combination therapy with VEGF antibody and cisplatin on murine B16F10 melanoma cells.
Our previous studies with EAC tumor model demonstrated that a VEGF polyclonal antibody combined with cisplatin inhibited tumor growth. Here we report the antitumor effect of VEGF antibody plus cisplatin on a murine metastatic tumor model specially emphasizing its effect on different angiogenic parameters both in vitro and in vivo. Mouse B16F10 melanoma cells were cultured in vitro in DMEM media containing 10% FBS, nonessential amino acids and antibiotics in a 5% CO(2) incubator at 37 degrees C and the effect of VEGF antibody singly and in combination with cisplatin on this cell was assessed by MTT assay, matrigel invasion study and MMP-9 expression study in vitro. In vivo studies were performed by two tumor models viz B16F10 solid tumor model and B16LuF10 lung tumor model. The mice treated with VEGF antibody (PAb) alone, cisplatin alone and combination of VEGF antibody and cisplatin on alternative days from the next day of tumor transplantation. Antitumor as well as antiangiogenic efficacy was monitored by measuring tumor burden, survivability, MVD measurement, serum NO value measurement and bcl-2 expression study. It was observed that administration of combined therapy with VEGF antibody and cisplatin augmented antitumor activity in B16F10 melanoma models than the either agents alone. Thus our experiments show a successful VEGF antibody based combination therapy with cisplatin and suggests that the enhancement of antitumor activity could be explained by a concomitant effect on both endothelial and tumor cell compartment.
Ghosh
Sonali
S
Department of Metabolic Regulation, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata-700026, India.
Maity
Putul
P
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009569:Nitric Oxide / Q000097:blood; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology
D000906:Antibodies; D061965:Matrix Metalloproteinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D002945:Cisplatin