Publikationsdatenbank

Oral simvastatin administration delays castration-resistant progression and reduces intratumoral steroidogenesis of LNCaP prostate cancer xenografts (2016)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Gordon, J. A.

Midha, A.

Szeitz, A.

Ghaffari, M.

Adomat, H. H.

Guo, Y.

Klassen, T. L.

Guns, E. S.

Wasan, K. M.

Cox, M. E.

Quelle

Prostate cancer and prostatic diseases

Bandzählung: 19

Heftzählung: 1

Seiten: 21 – 27

ISSN: 1476-5608

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/pcan201537

DOI: 10.1038/pcan.2015.37

Pubmed: 26238234

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Background:
Growing evidence supports the idea that de novo steroidogenesis has an important role in prostate cancer's progression to the castration-resistant state following androgen deprivation therapy. Therefore, reducing the availability of cholesterol for use as a precursor in androgen synthesis may reduce proliferation and disease progression.

Methods:
LNCaP xenograft-bearing mice were castrated and administered simvastatin via diet, and tumor volume and PSA concentration were monitored for 8 weeks post castration. Levels of serum and intratumoral androgens along with serum simvastatin and common toxicity markers were measured at end point.

Results:
Reduced post-castration tumor growth rate in simvastatin-treated mice correlated with delayed time to castration-resistant progression, determined by two serum PSA doublings from post-castration nadir, when compared with xenografts in mice on control diet. At 8 weeks post castration, serum simvastatin levels were comparable to clinically relevant human doses with no evidence of overt muscle or liver toxicity. This suppressed post-castration tumor growth in the simvastatin diet group was correlated with reduced intratumoral testosterone and dihydrotestosterone levels.

Conclusions:
Reduced tumor growth and intratumoral androgen levels observed in simvastatin-treated, castrated mice harboring LNCaP xenograft suggests that suppressing de novo steroidogenesis can delay castration-resistant progression of this tumor model.