sdz-psc-833 and Prostatic-Neoplasms

P-glycoprotein (P-gp) is commonly associated with multi-drug resistance (MDR) in cancer cells and the efflux of a broad spectrum of chemicals from the cell, including many chemotherapeutics and certain steroid hormones. The impact of P-gp and mechanisms involved in androgen transport and cellular accumulation within normal and malignant prostate cells remains unclear.. Following incubation of LNCaP, PC-3, HeLa, and HeLa FLAG-androgen receptor (AR) cells with (3)H-dihydrotestosterone (DHT) alone and in combination with P-gp inhibitors, PSC-833 and verapamil, we examined the cellular accumulation and efflux of androgens, as well as gene transcriptional response.. Our data reveal that the cellular transport and accumulation of DHT is dependent on the expression of functional AR and modulated by P-gp. P-gp over-expression by both transient transfection and aspirin treatment in LNCaP cells showed decreased intracellular DHT accumulation, further suggesting DHT efflux is P-gp regulated.. Androgen responsiveness may be modulated by P-gp in prostate cancer cells. The biological consequences of increased P-gp expression are decreased androgen accumulation and a corresponding decrease in androgen-regulated transcriptional activity and PSA gene expression.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Blotting, Northern; Blotting, Western; Cyclosporins; Dihydrotestosterone; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Male; Neoplasms, Hormone-Dependent; Precipitin Tests; Prostatic Neoplasms; Receptors, Androgen; RNA, Neoplasm; Verapamil