Trimetazidine alone or in combination with gemcitabine and/or abraxane decreased cell viability, migration and ATP levels and induced apoptosis of human pancreatic cells

Abstract

BackgroundTrimetazidine (TMZ) is an anti-ischemic agent that can inhibit the fatty acid oxidation. It has been stated that inhibition of fatty acid oxidation may be an acceptable approach to cancer treatment. MethodsWe examined the effects of TMZ alone or together with abraxane (ABX) and/or gemcitabine (GEM) on cell viability, apoptosis, adhesion, migration and ATP levels of human pancreatic cancer cell line PANC-1. ResultsTMZ significantly reduced the cell viability at higher concentrations. Lower cell viability values were found in cells co-treated with TMZ + GEM, TMZ + ABX and GEM + ABX. The combined treatment of TMZ with ABX and/or GEM significantly increased the apoptosis rates. The highest percentages of apoptosis were found in TMZ + ABX or TMZ + ABX + GEM treatments. TMZ alone or together with ABX and/or GEM significantly reduced the ATP levels. The lowest migration rates were also found at TMZ + ABX and TMZ + ABX + GEM treatments. ConclusionsOur study is the first study to indicate that TMZ can induce cytotoxicity and apoptosis and reduce migration and ATP levels, especially in cells co-treated with ABX and/or GEM. A combination strategy based on inhibition of fatty acid oxidation and anticancer drugs may be more effective in the treatment of pancreatic cancers.