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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-18184 |
| Date | 01 January 2010 |
| Creators | Chen, Tingting, Zhou, Gengyin, Zhu, Quan, Liu, Xian, Ha, Tuanzhu, Kelley, J. L., Kao, R. L., Williams, D. L., Li, Chuanfu |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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