Additive inhibitory effects of simvastatin and enzalutamide on androgen-sensitive LNCaP and VCaP prostate cancer cells.
We evaluated the effects of simvastatin and antiandrogen enzalutamide on growth and androgen signaling in androgen-sensitive LNCaP and VCaP prostate cancer cells. Simvastatin alone abolished androgen-induced growth in both cell lines but decreased androgen receptor (AR) and prostate-specific antigen protein expression only in LNCaP, indicating that statin-induced growth inhibition is beyond AR transcriptional activity in VCaP. Combination of simvastatin and enzalutamide exerted additive growth inhibition in both cell lines accompanied with strong induction of autophagy in LNCaP. The data provide new insight into statins' effects on androgen signaling and their proposed role in enhancing androgen deprivation therapy in prostate cancer.
University of Tampere, School of Medicine, Department of Anatomy, Tampere, Finland.
Heimo
H
Syvälä
University of Tampere, School of Medicine, Tampere, Finland. Electronic address: llpape@uta.fi.
Pasi
P
Pennanen
Tampere University Hospital, Department of Gastroenterology and Alimentary Tract Surgery and Tampere Pancreas Laboratory, Tampere, Finland.
Merja
M
Bläuer
University of Tampere, School of Medicine, Tampere, Finland; Tampere University Hospital, Department of Urology, Tampere, Finland.
Teuvo L J
TL
Tammela
University of Tampere, School of Medicine, Tampere, Finland; Tampere University Hospital, Department of Urology, Tampere, Finland.
Teemu J
TJ
Murtola
D000726:Androgen Antagonists / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D019821:Simvastatin / Q000494:pharmacology*; D016896:Treatment Outcome
D000726:Androgen Antagonists; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D019821:Simvastatin
Antiandrogen; Prostate cancer; Statin