Monoclonal antibodies targeting basic fibroblast growth factor inhibit the growth of B16 melanoma in vivo and in vitro.
Up-regulated basic fibroblast growth factor (bFGF or FGF-2) plays an important role in the development and metastasis of melanoma; therefore, neutralizing antibodies to bFGF may suppress melanoma growth. In this study, we have developed three monoclonal antibodies against bFGF (anti-bFGF mAbs), which display remarkable anti-tumor and anti-angiogenic effects in vitro and in vivo. Anti-bFGF mAbs significantly inhibit the proliferation and induce apoptosis of B16 cells, and show inhibitory effects on the migration of B16F10 cells and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Treatment of B16 melanoma spheroids with anti-bFGF mAbs in vivo results in significant reduction in tumor size and prolonged survival time of animals. Moreover, TUNEL (terminal transferase dUTP nick end labeling) assay and CD31 staining confirmed the increase of apoptosis and decrease of intratumoral microvessel density in tumor sections from animals treated with anti-bFGF mAbs. Our data indicate that anti-bFGF mAbs are potential therapeutic candidates for melanoma therapy by effectively suppressing the melanoma growth through inhibition of angiogenesis and induction of apoptosis in the tumor.
Li
Dan
D
Department of Immunology, Southern Medical University, Guangzhou 510515, PR China.
Wang
Hong
H
Xiang
Jun-Jian
JJ
Deng
Ning
N
Wang
Pan-Pan
PP
Kang
Yan-Li
YL
Tao
Jun
J
Xu
Meng
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016222:Fibroblast Growth Factor 2