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

Background: Trimetazidine (TMZ) is an anti-ischemic agent that can inhibit the fatty acid oxi-dation. It has been stated that inhibition of fatty acid oxidation may be an acceptable approach to cancer treatment. Methods: We 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. Results: TMZ significantly reduced the cell viability at higher concentrations. Lower cell via-bility 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. Conclusions: Our study is the first study to indicate that TMZ can induce cytotoxicity and apop-tosis 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. (c) 2021 Elsevier Masson SAS. All rights reserved.