Gene profiling of human VEGF signaling pathways in human endothelial and retinal pigment epithelial cells after anti VEGF treatment

BMC Research Notes

Adiel Barak¹  Anat Loewenstein¹  Gad Keren²  Daphna Mezad-Koursh¹  Sofia Maysel-Auslender²  Yonathan Semo²  Michal Entin-Meer²  Shani Golan¹ 

[1]Departments of Ophthalmology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, 64239, Israel

[2]Departments of Cardiology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel

关键词: PCR;    VEGF;    Gene expressions;    Ranibizumab;    Bevacizumab;   

Others  :  1129743
DOI  :  10.1186/1756-0500-7-617

 received in 2013-05-17, accepted in 2014-08-27,  发布年份 2014

【 摘 要 】

Background

Ranibizumab (Lucentis®) is a Fab-antibody fragment developed from Bevacizumab, a full-length anti-VEGF antibody. Both compounds are used for treating age-related macular degeneration (AMD). The influence of bevacizumab and ranibizumab on genes involved in signal transduction and cell signaling downstream of VEGF were compared in order to detect possible differences in their mode of action, which are not related to their Fab-antibody fragments.

Methods

Human umbilical vein cell lines (EA.hy926) and retinal pigment epithelial cells (ARP-19) were exposed to oxidative stress. The cells were treated with therapeutic concentrations of bevacizumab (0.25 mg/mL) and ranibizumab (125 mg/mL) for 24 hours prior to all experiments, and their effects on gene expressions were determined by RT- PCR.

Results

After exposure to bevacizumab, more genes in the endothelial cells were up-regulated (KDR, NFATc2) and down-regulated (Pla2g12a, Rac2, HgdC, PRKCG) compared to non-treated controls. After exposure to ranibizumab, fewer genes were up-regulated (PTGS2) and down-regulated (NOS3) compared to controls. In comparison between drugs, more genes were up-regulated (NFATc2 and KDR) and more were down-regulated (Pla2g12a, Pla2g1b, Ppp3r2, Rac2) by bevacizumab than by ranibizumab. In RPE cells, NOS3 and PGF were up-regulated and Pla2g12b was down-regulated after exposure to ranibizumab, while PIK3CG was up-regulated and FIGF was down-regulated after exposure to bevacizumab, but the differences in gene expression were minor between drugs (PIK3CGand PGF were down-regulated more by ranibizumab than by bevacizumab).

Conclusions

The different gene expressions after exposure to ranibizumab and bevacizumab in endothelial and RPE cells may indicate a somewhat different biological activity of the two compounds.

【 授权许可】

   
2014 Golan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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