The obeticholic acid can positively regulate the cancerous behavior of MCF7 breast cancer cell line

Abstract

Background: The diagnosis and treatment processes of cancer are among the main challenges of medical science in recent decades. The use of different therapeutic agents is one of the most common methods frequently utilized for cancer treatment. Accumulating evidence points to a potential effect of Obeticholic acid (OCA), a specific ligand for farnesoid X receptor, on the regulation of cancer-associated pathways. In spite of tremendous efforts to introduce OCA into the clinical setting, there is a great deal of uncertainty about its impact on breast cancer treatment. This study was performed to evaluate the effects of OCA on breast cancer.

Methods and results: In this experiment, the MCF-7 (Michigan Cancer Foundation-7) cell line was treated with 0.1 µM OCA, and cancerous characteristics of the MCF-7 cell line was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide) assay, gelatin zymography, western blot, Real-time PCR, flow cytometry, and ELISA techniques. The results indicated that OCA increased the rate of apoptosis and the expression levels of PPARα (Peroxisome proliferator-activated receptor alpha) and TIMP-1 (tissue inhibitor of metalloproteinase-1) genes in this cell line, while it reduced the mRNA levels of MMP7 (matrix metalloproteinase 7) and Bcl-2 (B-cell lymphoma 2) genes, as well as the protein levels of the active form of AKT (protein kinase B), Erk1/2 (extracellular signal-regulated kinase 1/2) and STAT3 (Signal transducers and activators of transcription-3). Also, OCA decreased the activity of MMP9, while it increased the secretion of VEGF-A (vascular endothelial growth factor-A).

Conclusions: It seems that OCA can exert anti-cancer effects on the MCF-7 cells by reducing growth, proliferation, migration, invasion, and regulation of the expression of genes involved in cancer-associated pathways. However, it should be noted that further studies are warranted to establish this concept, especially the increase of VEGF-A can be considered a challenge for the results of this study.

Keywords: Breast cancer; FXR; MCF7; Obeticholic acid.