Mitogen-Activated Protein Kinases Pathways Mediate the Sunitinib-Induced Hypertrophy in Rat Cardiomyocyte H9c2 Cells

摘要: Sunitinib (SUN) is a multi-targeted tyrosine kinase inhibitor used for the treatment of gastrointestinal stromal tumors and renal cell carcinoma. Cardiotoxicity has been reported as significant side effect associated with SUN treatment, yet mechanism poorly understood. The main purpose this study was to investigate potential effects on cardiac hypertrophic genes role mitogen-activated protein kinases (MAPKs) signaling pathway in rat cardiomyocyte H9c2 line. In present study, real-time quantitative polymerase chain reaction showed that cells increasing concentrations (0, 1, 2.5, 5 µM) significantly induced gene markers, such brain natriuretic peptides (BNP) myosin heavy (β-MHC α-MHC) concentration- time-dependent manners. onset mRNA induction observed early 9 h remained elevated at least 18 after µM. At level, Western blot analysis increased BNP β-MHC, while it inhibited α-MHC levels concentration-dependent manner. These SUN-mediated were increase size hypertrophy by approximately 70 % highest concentration, Importantly, inhibition MAPK using SB203580 (p38 inhibitor), U0126 (extracellular signal-regulated SP600125 (c-Jun NH2-terminal inhibitor) potentiated SUN-induced β-MHC levels, but did alter level. Whereas inhibitors generally decreased BNP, whereas only SB U0 no α-MHC, which decrease size. Together, these results indicate expression through MAPK-dependent mechanisms.