P37 The assessment of the cardioprotective properties of metformin during sunitinib-induced cytotoxicity

Multi-tyrosine kinase inhibitor Sunitinib is associated with cardiotoxicity, in contrast the anti-type-2 diabetic Metformin is associated with cardioprotective properties via adenosine monophosphate-activated protein kinase (AMPK) activation.We investigated whether treatment of rat langendorff hearts with Metformin attenuated Sunitinib-induced cytotoxicity via AMPK. We further investigated the cotreatment of Metformin with Sunitinib using HepG2 and HL60 cancer cell lines to reveal if potential adjunctive therapy drugs interfere with and prevent the anti-cancer activity of chemotherapy agents.Male Sprague-Dawley rat hearts were Langendorff perfused with vehicle or, Sunitinib (1 µM) in the absence or presence ±Metformin (50 µM)±S-4-Nitro-benzyl-theonosine (AMPK inhibitor, NBTI) (1 µM) for 155 min. Functional parameters were measured throughout the experiment (n=6), heart tissue was also assessed for necrosis or relevant protein phosphorylation (n=6).HepG2 and HL60 cells treated in the presence of Sunitinib (0.1–100 µM)±Metformin (50/1000 µM)±NBTI (1 µM) (n=6) were assessed for cell viability..Sunitinib caused a significant increase in myocardial infarcted tissue (Vehicle=11%±1% vs Sunitinib=31±2%, p