Effects of Bicalutamide and 4OH-Tamoxifen on Androgen-regulated Gene Expression in the LNCaP Cell Line

• Published in: Anticancer research 2012-12, Vol.32 (12), p.5323-5329
• Main Authors: MANGERINI, Rosa, ARGELLATI, Francesca, PFEFFER, Ulrich, BOCCARDO, Francesco
• Format: Article
• Language: English
• Subjects: Androgens - physiology; Anilides - administration & dosage; Anilides - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biological and medical sciences; Cell Growth Processes - drug effects; Cell Growth Processes - genetics; Cell Line, Tumor; Gene Expression Regulation, Neoplastic - drug effects; Humans; Kallikreins - biosynthesis; Male; Medical sciences; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - genetics; Nephrology. Urinary tract diseases; Nitriles - administration & dosage; Nitriles - pharmacology; Prostate-Specific Antigen - biosynthesis; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Tamoxifen - administration & dosage; Tamoxifen - analogs & derivatives; Tamoxifen - pharmacology; Tosyl Compounds - administration & dosage; Tosyl Compounds - pharmacology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0250-7005; 1791-7530

Bicalutamide (BIC) is an alternative treatment to castration for advanced prostate cancer. Breast events are common adverse effects which can be effectively prevented by the concurrent administration of tamoxifen, a selective estrogen receptor modulator. We investigated the effects of BIC, 4-hydroxy Tamoxifen (4OHT), the active metabolite of tamoxifen, and their combination on the expression of a panel of genes implicated in prostate cancer development and progression in LNCaP cells stimulated with dihydrotestosterone. Our findings confirm the anti-proliferative activity of BIC on LNCaP cell growth but also show the down-regulating function of this anti-androgen on the expression of genes involved in tumor proliferation and invasion [cyclins, caspases, epidermal growth factor (EGF)]. The combination with 4OHT exerts a synergistic effect on the downregulation of some genes involved in prostate cancer progression. The observation that the expression of several genes [such as B-cell lymphoma-2 (BCL2), myelocytomatosis oncogene (MYC), caspases] is modulated midly-to-moderately, after 4OHT addition suggests that this combined approach in the clinical setting should be further investigated through appropriate trials.