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

摘要

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<0.0001).No significant differences in the phenotype of phosphatidylserine,tissue factor or basigin expression were detected at therapeutic doses(P>0.05).Apoptosis was significantly increased following incubation with CAY10566(P<0.05).Fatty acid content of cells was significantly higher following gemcitabine treatment compared to CAY10566 alone or gemcitabine+CAY10566(P<0.05).Platelet-derived growth factor released by gemcitabine-treated cells was significantly increased compared to 142 nM CAY10566 alone or gemcitabine+CAY10566(P<0.01).CAY10566 did not affect the size of isolated tumor cells but gemcitabine+CAY10566 significantly increased the size compared to the control(P<0.05).Cell viability decreased significantly after the treatment with gemcitabine+CAY10566 compared with CAY10566 alone(P<0.05)and gemcitabine alone(P<0.01).However,when cycles of chemotherapy were mimicked and treatment was removed,the number of cell viability was significantly reduced(P<0.05).Conclusion:This study suggests that CAY10566 may be a suitable supplement for gemcitabine chemotherapy for PC.