Liver X receptor activation inhibits PC-3 prostate cancer cells via the beta-catenin pathway

• Published in: Pathology, research and practice research and practice, 2017-03, Vol.213 (3), p.267-270
• Main Authors: Youlin, Kuang, Li, Zhang, Weiyang, He, Jian, Kang, Siming, Liang, Xin, Gou
• Format: Article
• Language: English
• Subjects: Agonist; Apoptosis - drug effects; beta Catenin - metabolism; Beta-catenin; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin D1 - metabolism; Humans; Hydrocarbons, Fluorinated - pharmacology; Liver X receptors; Liver X Receptors - metabolism; Male; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-myc - metabolism; Signal Transduction - physiology; Sulfonamides - pharmacology
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2016.04.013

Liver X receptors (LXRs) are nuclear receptors family of ligand-dependent transcription factors that play a crucial role in regulating cholesterol metabolism and inflammation. Recent studies show that LXR agonists exhibit anti-cancer activities in a variety of cancer cell lines including prostate. To further identify the potential mechanisms of LXRα activation on prostate cancer, we investigated the effect of LXR agonist T0901317 on PC3 prostate cancer cell and in which activity of beta-catenin pathway involved. Prostate cancer PC3 cells were transfected with LXR-a siRNA and treated with LXR activator T0901317. qRT-PCR and western blot were used to detect the LXR-a expression. beta-catenin, cyclin D1 and c-MYC were analyzed by western blot. Cell apoptosis was examined by flow cytometry and Cell proliferation was assessed by Cell Counting Kit-8 assay. Cell migration was detected by Transwell chambers. Data showed that T0901317 significantly inhibited PC3 cell proliferation as well as invasion and increased apoptosis in vitro. Furthermore, we found that LXRα activation induced the reduction of beta-catenin expression in PC3 cells, and this inhibitory effect could be totally abolished when cells were treated with LXRα. Meanwhile, the expression of beta-catenin target gene cyclin D1 and c-MYC were also decreased. This study provided additional evidence that LXR activation inhibited PC-3 prostate cancer cells via suppressing beta-catenin pathway.