Effects of Bevacizumab on Bcl-2 Expression and Apoptosis in Retinal Pigment Epithelial Cells under Oxidative Stress.
10.3341/kjo.2015.29.6.424
- Author:
Sukjin KIM
1
;
Young Jun KIM
;
Na Rae KIM
;
Hee Seung CHIN
Author Information
1. Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, Korea. hschin@inha.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Apoptosis;
Bcl-2;
Bevacizumab;
Retinal pigment epithelial cell
- MeSH:
Angiogenesis Inhibitors/*pharmacology;
Apoptosis/*drug effects;
Bevacizumab/*pharmacology;
Cell Line;
Enzyme-Linked Immunosorbent Assay;
Flow Cytometry;
Gene Expression Regulation/physiology;
Humans;
Hydrogen Peroxide/toxicity;
Oxidative Stress/drug effects;
Proto-Oncogene Proteins c-bcl-2/*genetics;
RNA, Messenger/genetics;
Real-Time Polymerase Chain Reaction;
Retinal Pigment Epithelium/*drug effects/metabolism/pathology;
Vascular Endothelial Growth Factor A/antagonists & inhibitors
- From:Korean Journal of Ophthalmology
2015;29(6):424-432
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: To evaluate the effects of bevacizumab on expression of B-cell leukemia/lymphoma (Bcl)-2 and apoptosis in retinal pigment epithelial (RPE) cells under oxidative stress conditions. METHODS: RPE cells were treated with H2O2 (0, 100, 200, 300, and 400 microM) and bevacizumab at or above the doses normally used in clinical practice (0, 0.33, 0.67, 1.33, and 2.67 mg/mL). Cell apoptosis was measured using flow cytometry with annexin V-fluorescein isothiocyanate. The expression of Bcl-2 mRNA was determined using reverse transcription polymerase chain reaction. RESULTS: Under low oxidative stress conditions (H2O2 100 microM), cell apoptosis was not significantly different at any concentration of bevacizumab, but Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL). Under moderate oxidative stress conditions (H2O2 200 microM), Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL), but cell apoptosis increased only at 2.67 mg/mL of bevacizumab. Under high oxidative stress (300 microM) conditions, cell apoptosis increased at high concentrations of bevacizumab (1.33 and 2.67 mg/mL), but it did not correlate with Bcl-2 expression. CONCLUSIONS: Withdrawal of vascular endothelial growth factor can lead to RPE cell apoptosis and influences the expression of anti-apoptotic genes such as Bcl-2 under oxidative stress conditions. Since oxidative stress levels of each patient are unknown, repeated injections of intravitreal bevacizumab, as in eyes with age-related macular degeneration, might influence RPE cell survival.
