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Calcitriol (1,25-Dihydroxycholecalciferol) Potentiates Activity of Mitoxantrone/Dexamethasone in an Androgen Independent Prostate Cancer Model

2002; Lippincott Williams & Wilkins; Volume: 168; Issue: 2 Linguagem: Inglês

10.1016/s0022-5347(05)64740-4

1527-3792

Sharmila Ahmed, Candace S. Johnson, Robert M. Rueger, Donald L. Trump,

FOXO transcription factor regulation

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Aug 2002Calcitriol (1,25-Dihydroxycholecalciferol) Potentiates Activity of Mitoxantrone/Dexamethasone in an Androgen Independent Prostate Cancer Model Sharmila Ahmed, Candace S. Johnson, Robert M. Rueger, and Donald L. Trump Sharmila AhmedSharmila Ahmed , Candace S. JohnsonCandace S. Johnson , Robert M. RuegerRobert M. Rueger , and Donald L. TrumpDonald L. Trump View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64740-4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Mitoxantrone combined with glucocorticoids is widely used for androgen independent prostate cancer. It is well tolerated, reduces prostate specific antigen, diminishes pain and improves quality of life. Calcitriol (1,25-dihydroxycholecalciferol) inhibits proliferation, modulates cell cycle progression, induces apoptosis and potentiates the cytotoxic effects of a number of agents. Glucocorticoids potentiate the antitumor effects of calcitriol and blunt calcitriol induced hypercalcemia. Therefore, we investigated the effect of calcitriol on the antitumor efficacy of mitoxantrone and dexamethasone or mitoxantrone/dexamethasone in the PC-3 androgen independent prostate cancer model. Materials and Methods: We treated PC-3 cells in vitro with various concentrations of mitoxantrone/dexamethasone with and without calcitriol, and assessed growth inhibition by crystal violet assays. We similarly treated mice bearing PC-3 xenografts and performed excision clonogenic assays and tumor outgrowth studies to assess antitumor activity. Results: Calcitriol significantly increased mitoxantrone/dexamethasone mediated growth inhibition in PC-3 cells (p <0.05). Median dose effect analysis indicated that calcitriol is synergistic with mitoxantrone. Adding calcitriol to mitoxantrone/dexamethasone significantly reduced the surviving fraction per gm. tumor compared with mitoxantrone/dexamethasone or untreated controls (p <0.03). Calcitriol plus mitoxantrone/dexamethasone also caused significantly greater tumor regression in PC-3 xenografts compared with treatment with mitoxantrone/dexamethasone or untreated controls (p <0.02). Conclusions: These preclinical data demonstrate that calcitriol increases the antitumor activity of mitoxantrone/dexamethasone in the PC-3 model system. This combination may be efficacious for prostate cancer. References 1 : Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol1999; 17: 2506. 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Androgen-independent prostate cancer (AIPC) treatment with weekly high-dose calcitriol and docetaxel. Proc Am Soc Clin Oncol, abstract 707, 2002 Google Scholar From the Departments of Medicine, Pharmacology and Urology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 168Issue 2August 2002Page: 756-761 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordsmitoxantronedexamethasonevitamin Dprostatic neoplasmsprostateMetricsAuthor Information Sharmila Ahmed More articles by this author Candace S. Johnson More articles by this author Robert M. Rueger More articles by this author Donald L. Trump More articles by this author Expand All Advertisement PDF downloadLoading ...