VEGF antibody plus cisplatin reduces angiogenesis and tumor growth in a xenograft model of ovarian cancer.
In our previous study, PAb, a VEGF polyclonal antibody was found to inhibit murine tumor growth significantly. The main objective of this study was to investigate the efficacy of combination therapy of (PAb) and cisplatin on human ovarian cancer xenograft. Effect of VEGF, PAb, PAb-cisplatin combination, and cisplatin alone on cultured human ovarian teratocarci-noma cell line PA-1 were assessed by measuring cell proliferation, matrigel invasion, MMP-9 expression, and MMP-9 secretion. In vivo, effect of PAb was observed in a xenograft model of ovarian cancer. Antitumor efficacy was monitored by assessment of tumor volume, MVD, serum NO, serum VEGF, and p53 expression. VEGF increased proliferation of PA-1 cell in a dose-dependent manner while addition of PAb inhibited cell proliferation, cell invasion as well as MMP-9 secretion in vitro. Tumor burden in PAb and PAb-cisplatin combination group was reduced by 41% (p < 0.05) and 66% (p < 0.01), respectively. A significant decrease in MVD, serum NO, serum VEGF, and p53 expression was also observed after PAb and PAb-cisplatin combination treatment when compared to normal mouse serum IgG-treated control mice. Thus, it was concluded that VEGF immunoneutralization may enhance cisplatin-in-duced apoptosis in human ovarian cancer and thus may be an effective way to reduce tumor growth in ovarian carcinoma.
Department of Metabolic Regulation, Chittaranjan National Cancer Institute, 37, S P Mukherjee Road, Kolkata-700026, India.
Sonali
S
Ghosh
Putul
P
Maity
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D009569:Nitric Oxide / Q000097:blood; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D018243:Teratocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D019138:Antibodies, Blocking; D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D009569:Nitric Oxide; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002945:Cisplatin