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Study of anti‐proliferative activity of ranibizumab, bevacizumab, pegaptanib and aflibercept on fibroblast‐like cell strain in vitro
Author(s) -
LYTVYNCHUK L
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.1672.x
Subject(s) - fibroblast , apoptosis , cell growth , mitotic index , ranibizumab , basic fibroblast growth factor , pegaptanib , in vitro , medicine , microbiology and biotechnology , pharmacology , biology , cancer research , mitosis , growth factor , bevacizumab , biochemistry , receptor , chemotherapy
Purpose To evaluate the anti‐proliferative action of drugs that block vascular endothelial growth factor (anti‐VEGF: ranibizumab, bevacizumab, pegaptanib and aflibercept) upon fibroblast‐like cells, as in vitro model for studying their implication on fibroblast‐containing choroidal neovascular membranes (CNV). Methods The cellular anti‐proliferative effects of the four anti‐VEGFs (cellular survival, mitotic‐ and polykaryocyte index, level of apoptosis) were evaluated over 5 days on the fibroblast‐like cell strain L929. Cellular growth‐kinetics indices (specific growth velocity (µ), population number doubling time (td) and reproduction velocity (n)) were calculated and used to reveal dose‐dependence of their anti‐proliferative activity. Results The anti‐VEGFs could inhibit cellular survival, mitotic activity, and increase cellular heterogeneity of L929 cells in a dose‐dependent manner. The anti‐proliferative activity of the anti‐VEGFs was dose‐dependent, while the apoptosis level was proportional to the dose increase in all four cases. The cellular growth‐kinetics distinguished ranibizumab for having less aggressive anti‐proliferative action with increasing doses, which was due to compensation of cell death by proliferation; the rest of the anti‐VEGFs had anti‐proliferative and apoptotic activity prevail the cellular survival. Different concentrations of aflibercept caused insignificant effect upon the cellular mitotic index compared to controls. Conclusion All four anti‐VEGF drugs exhibited marked anti‐proliferative and apoptotic activity upon fibroblast‐like cells in vitro. Overall, the explored effects might explain the fibroblast‐like response to anti‐VEGF drugs in vivo and be the cause for involution of CNVs.