Modulatory Effects of Metformin on Farnesoid X receptor and Specificity Protein 1 in Human Pancreatic Cancer BxPC-3 Cells

Abstract

Background: Pancreatic cancer is the fourth major cause of death, accounting for 7% of cancer-related deaths. Metformin (antihyperglycemic agent) users had a 62% lower risk of developing pancreatic cancer when compared to metformin non-users. Objective: This research aims to study the role of the Farnesoid X receptor (FXR) receptor in human pancreatic cancer cell line BxPC-3 and metformin’s modulatory effects on this receptor. Material and methods: Cell viability was assessed using MTT assay for INT747 (FXR agonist) and metformin, FXR and Specificity Protein 1 (Sp1) mRNA and protein levels were measured by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blot, respectively. Results: INT747 increased the growth and viability of BxPc-3 cells in addition to a significant increase in FXR and SP1 mRNA and protein levels. In contrast, BxPC-3 cells viability was significantly reduced by metformin in a dose- and time-dependent manner with downregulation of FXR and SP1 at mRNA and protein levels Conclusion: FXR may act as an oncogenic factor in pancreatic cancer BxPC-3 cells by increasing FXR and SP1 expression, while metformin significantly reduced FXR mRNA and protein levels in BxPC-3 cells, which may be due to a reduction in SP1 expression.