Stearoyl-CoA desaturase 1 inhibitor supplemented with gemcitabine treatment reduces the viability and fatty acid content of pancreatic cancer cells in vitro

Abstract

Abstract Objective: Pancreatic cancer (PC) is an aggressive cancer with ineffective treatment. Inhibition of stearoyl-CoA desaturase 1 (SCD1) suppresses cancer proliferation and might act as a novel chemotherapy supplement, but this has not been investigated in PC. Here, the effects of SCD1 inhibitor CAY10566 supplemented with gemcitabine treatment (gemcitabine+CAY10566) on PC cell viability, apoptosis, phenotype, fatty acid content, platelet-derived growth factor release, and cell size were investigated. Methods: Human PC cell line (PANC-1) was treated with SCD1 inhibitor CAY10566 with or without gemcitabine. Cell viability was assayed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and apoptosis and phenotype were determined using flow cytometry. Fatty acid content and platelet-derived growth factor release were measured by enzyme-linked immunosorbent assay. Cell size was determined using scanning electron microscopy. Results: Half-maximal inhibitory concentration of gemcitabine or CAY10566 significantly reduced PANC-1 viability compared to gemcitabine alone (P < .0001). No significant differences in the phenotype of phosphatidylserine, tissue factor or basigin expression were detected at therapeutic doses (P > .05). Apoptosis was significantly increased following incubation with CAY10566 (P < .05). Fatty acid content of cells was significantly higher following gemcitabine treatment compared to CAY10566 alone or gemcitabine+CAY10566 (P < .05). Platelet-derived growth factor released by gemcitabine-treated cells was significantly increased compared to 142 nM CAY10566 alone or gemcitabine+CAY10566 (P < .01). CAY10566 did not affect the size of isolated tumor cells but gemcitabine+CAY10566 significantly increased the size compared to the control (P < .05). Cell viability decreased significantly after the treatment with gemcitabine+CAY10566 compared with CAY10566 alone (P < .05) and gemcitabine alone (P < .01). However, when cycles of chemotherapy were mimicked and treatment was removed, the number of cell viability was significantly reduced (P < .05). Conclusion: This study suggests that CAY10566 may be a suitable supplement for gemcitabine chemotherapy for PC.