Overexpression of Vascular Endothelial Growth Factor 165 (VEGF165) Protects Cardiomyocytes Against Doxorubicin-Induced Apoptosis
Document Type
Article
Publication Date
1-1-2010
Description
Doxorubicin (Dox) has been employed in cancer chemotherapy for a few decades. However its clinical application became restricted because of dose-dependent cardiomyopathy. Recent studies suggest that Dox-induced cardiomyocyte apoptosis is a primary cause of cardiac damage. Vascular endothelial growth factor (VEGF) is a major factor for endothelial cell survival and angiogenesis. We have previously shown that VEGF16S significantly attenuates oxidative stress-induced cardiomyocytes apoptosis. We hypothesized that VEGF165 will protect the cardiomyocytes from Dox-induced apoptosis. To evaluate our hypothesis, we transfected cardiomyocytes H9c2 with adenovirus expressing VEGF16S 24 hours before the cells were challenged with Dox at a concentration of 2 uM. Cardiomyocyte apoptosis was evaluated by Annexin V-FITC staining and by Western blot detection of cleaved caspase-3. The hypothesis was confirmed, and the protective mechanisms involve the inhibition of death receptor-mediated apoptosis and up-regulation of the prosurvival Akt/NF-κB/BcI-2 signaling pathway.
Citation Information
Chen, Tingting; Zhou, Gengyin; Zhu, Quan; Liu, Xian; Ha, Tuanzhu; Kelley, J. L.; Kao, R. L.; Williams, D. L.; and Li, Chuanfu. 2010. Overexpression of Vascular Endothelial Growth Factor 165 (VEGF165) Protects Cardiomyocytes Against Doxorubicin-Induced Apoptosis. Journal of Chemotherapy. Vol.22(6). 402-406. https://doi.org/10.1179/joc.2010.22.6.402 PMID: 21303748 ISSN: 1120-009X