Combination of bevacizumab and irradiation on uveal melanoma: an in vitro and in vivo preclinical study.
BACKGROUND
Radiotherapy (RT) is the standard treatment for uveal melanoma. However it can cause damage to the retina and optic nerve. This study examined the in vitro and in vivo effects of the anti-VEGF monoclonal antibody bevacizumab associated with radiotherapy (RT) on tumor growth and tumor proliferation and vasculature on OCM-1 human uveal melanoma cell line.


METHODS
The anti-proliferative effects of bevacizumab, RT and their combination were tested both in vitro (OCM-1 cells co-cultured with HUVEC cells in Transwell plates) and in vivo (OCM-1 tumor xenografts in nude mice). In addition, treatment effects in vitro on VEGF secretion, as well as treatment effects in vivo on tumor proliferation (Ki67 labelling), tumor vasculature (VEGFR2 labelling) and VEGF tumoral concentration were analyzed.


RESULTS
Bevacizumab given alone had a significant impact on tumor growth in vivo (and moderate effects in vitro). The bevacizumab-RT combination had additive effects in vitro (tumor cell proliferation) and in vivo (tumor growth), which translated into a significant decrease in Ki67 expression, VEGFR2 labelling and VEGF tumoral content.


CONCLUSIONS
The bevacizumab-RT combination could be a promising clinical option to explore for the management of human uveal melanoma, since it may allow RT dose reduction without loss of antitumor efficacy.
Pathology unit, Centre Antoine Lacassagne, 33 Av de Valombrose, 06189 Nice cedex 2, France.
Anne
A
Sudaka
Antoine
A
Susini
Cristiana
C
Lo Nigro
Jean-Louis
JL
Fischel
Nicolas
N
Toussan
Patricia
P
Formento
Federica
F
Tonissi
Laura
L
Lattanzio
Elvio
E
Russi
Marie-Christine
MC
Etienne-Grimaldi
Marco
M
Merlano
Gérard
G
Milano
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D047368:Tumor Burden / Q000187:drug effects; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000098943:Uveal Melanoma
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab