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Bevacizumab modulates the process of fibrosis in vitro
Author(s) -
Zhang Min,
Chu Sanjun,
Zeng Fanxing,
Xu Haifeng
Publication year - 2015
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.12374
Subject(s) - ctgf , medicine , vascular endothelial growth factor , growth factor , basic fibroblast growth factor , fibrosis , transforming growth factor , umbilical vein , connective tissue , bevacizumab , cancer research , microbiology and biotechnology , endocrinology , pathology , in vitro , chemistry , biology , biochemistry , receptor , chemotherapy , vegf receptors
Background Fibrosis is the most common side effect after anti‐vascular epithelial growth factor (VEGF) therapy (intravitreal bevacizumab) for retinal or choroidal neovascularization. This study was to investigate the efficacy of bevacizumab on the expressions of fibrosis‐related cytokines in human umbilical vein endothelial cells ( HUVEC s) in vitro . Methods Cultured HUVEC s were divided into groups of controls (group 1), hypoxia (group 2) and hypoxia combined with bevacizumab (group 3). No treatment was given in group 1. In group 2, cobalt(II) chloride ( CoCl 2 ) (200 μm) was added to the medium. In group 3, in addition to CoCl 2 , bevacizumab was mixed in the medium, with a final concentration of 0.25 mg/mL, roughly equal to the concentration used clinically. The expressions of connective tissue growth factor ( CTGF ), transforming growth factor‐β 2 ( TGF ‐β 2 ) and basic fibroblast growth factor‐2 ( bFGF ‐2) were evaluated by SYBR green real‐time polymerase chain reaction ( PCR ) and enzyme‐linked immunosorbent assay at 6 h, 12 h, 24 h and 48 h. Matrix metalloproteinases ( MMP) ‐2 was detected by SYBR green real‐time PCR and Western blotting at each time point. Results Both messenger RNA and protein levels of CTGF , bFGF , TGF ‐β 2 and MMP ‐2 in group 2 were higher than group 1 ( P < 0.05). In group 3, the expressions of CTGF , bFGF , TGF ‐β 2 and MMP ‐2 were upregulated compared with group 2 ( P < 0.05).Conclusions Bevacizumab at clinical doses can exert pro‐fibrotic effects on HUVEC s by upregulating the expressions of CTGF , bFGF , TGF ‐β 2 and MMP ‐2. This may be involved in fibrosis after anti‐ VEGF therapy.