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

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dc.cclicenceCC-BY-NCen
dc.contributor.authorHackney, A. B.
dc.contributor.authorChung, W. Y.
dc.contributor.authorIsherwood, J.
dc.contributor.authorDennison, A. R.
dc.contributor.authorMartin, N.
dc.date.acceptance2021-12
dc.date.accessioned2022-02-01T11:47:47Z
dc.date.available2022-02-01T11:47:47Z
dc.date.issued2021-12
dc.descriptionopen access articleen
dc.description.abstractObjective: 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 142nM 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.en
dc.funderNo external funderen
dc.identifier.citationHackney, Amon B., Chung, Wen Y., Isherwood, J., Dennison, A.R., Martin, N. (2021) Stearoyl-CoA desaturase 1 inhibitor supplemented with gemcitabine treatment reduces the viability and fatty acid content of pancreatic cancer cells in vitro. Journal of Pancreatology: 4 (4) pp. 170-177en
dc.identifier.doihttps://doi.org/10.1097/JP9.0000000000000082
dc.identifier.urihttps://hdl.handle.net/2086/21651
dc.language.isoenen
dc.peerreviewedYesen
dc.publisherWolters Kluweren
dc.subjectGemcitabineen
dc.subjectMetabolomicsen
dc.subjectPancreatic canceren
dc.subjectSCD1 inhibitoren
dc.subjectViabilityen
dc.titleStearoyl-CoA desaturase 1 inhibitor supplemented with gemcitabine treatment reduces the viability and fatty acid content of pancreatic cancer cells in vitroen
dc.typeArticleen

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