The role of quercetin in modulating lipid metabolism and enhancing chemotherapy via the STAT3-CPT1B pathway in pancreatic cancer

Background: Pancreatic Cancer is a highly aggressive gastrointestinal tumor with limited treatment options, such as surgery and chemotherapy. Thus, further research into its pathogenesis and new treatments is necessary.

Methods: Fluorescence-activated cell sorting was employed to sort pancreatic Cancer Stem Cells (PCSCs). Sphere formation assays and Cell Counting Kit-8 (CCK-8) assays were conducted to assess stemness and proliferation capacity. Quantitative Real-Time PCR and Western blot analysis were employed to assess gene expression levels. Furthermore, immunofluorescence microscopy and chromatin immunoprecipitation assays were conducted to examine alterations in signaling pathways and gene expression.

Results: Quercetin and gemcitabine may inhibit PANC-1 cells and PCSCs by affecting energy metabolism. Chromatin immunoprecipitation assays revealed an interaction between STAT3 and CPT1B in PCSCs. Quercetin and gemcitabine might affect energy metabolism by inhibiting STAT3 and CPT1B. Manipulating STAT3 expression (overexpression plasmids and siRNA knockdown) altered CPT1B mRNA and protein expression. Although acetyl-CoA reversed the quercetin- and gemcitabine-induced expression of N-Cadherin, DECR1, and ALDH, it had minimal influence on CPT1B and STAT3 levels.

Conclusion: Quercetin inhibits the expression of CPT1B via the STAT3 signaling pathway, affecting lipid metabolism and exerting antitumor effects. Furthermore, the combined administration of quercetin and gemcitabine exhibits enhanced therapeutic efficacy.

Energy metabolism; Gemcitabine; Pancreatic cancer; Quercetin; STAT3 signaling pathway.