Abstract
Prostate cancer (PCa) is the second most frequently diagnosed cancer of men and the fifth most common cancer overall in the world. Surgeries, such as radical prostatectomy or transurethral resection of the prostate (TURP), are often successful for organ-confined prostate cancer. However, approximately 15% to 30% of patients with localized disease receiving surgery develop relapsed tumors within 5 to 10 years. Most of these patients subsequently show poor therapeutic outcome. More than 80% of patients died from PCa developed bone metastases. Liver X receptors (LXRs) belong to the nuclear receptor superfamily and LXR regulates the homeostasis of cholesterol, fatty acids and glucose. We previously reported that LXR agonist treatment suppresses proliferation of PCa cells via induction of G1 cell cycle arrest. In this study, we demonstrated that LXR agonist T0901317 treatment suppressed migration and invasion of PC-3 and DU-145 human prostate cancer cells. Metastasis of PC-3 xenografts in nude mice was reduced by oral administration of T0901317. Micro-Western Array (MWA) is an antibody-based modified reverse phase array composes of a GeSim Nanoplotter arrayer, a GE multiphor, and a Licor Odyssey scanner. Micro-Western Array allows detecting protein expression level or phosphorylation status change of 96-384 different antibodies in 6-15 samples simultaneously. Micro-Western Array study and immunohistochemistry (IHC) staining indicated that T0901317 treatment reduced signaling proteins involved in regulation of cell proliferation and epithelial-to-mesenchymal transition (EMT), including Akt, NFκB, c-Myc, and snail. Our observations suggested that LXR agonists may be a potential candidate for prevention and inhibition of prostate cancer metastasis.