5-aza-2'-deoxycytidine delays androgen-independent disease and improves survival in the transgenic adenocarcinoma of the mouse prostate mouse model of prostate cancer

Clin Cancer Res. 2007 Apr 1;13(7):2136-43. doi: 10.1158/1078-0432.CCR-06-2381.


Purpose: We have previously shown that 5-aza-2'-deoxycytidine (5-aza) is an effective chemopreventive agent capable of preventing early disease progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The purpose of this study was to determine the effect of 5-aza on preexisting TRAMP prostate cancers and prevention of androgen-independent prostate cancer.

Experimental design: TRAMP mice with established prostate cancers were treated with 5-aza, castration, castration + 5-aza, or vehicle control (PBS). One cohort of 22 mice per treatment was euthanized after 10 weeks of treatment, whereas a second cohort of 14 mice per group was followed until death to determine survival. Histologic sections of prostate, pelvic lymph nodes, lung, and liver were blinded and analyzed by a certified genitourinary pathologist (K.J.W.).

Results: Combined treatment (castration + 5-aza) provided significant survival benefits over either single treatment (combined versus castration P = 0.029, combined versus 5-aza P = 0.036). At 24 weeks of age, 86% of mice within the PBS cohort exhibited histologic evidence of prostate cancer, whereas only 47% of the combined cohort exhibited malignant disease (P < 0.0001). Additionally, whereas 43% of the PBS treatment group exhibited lymph node metastases, these were only observed in 21% of the combined treatment mice.

Conclusions: This is the first study to examine the effect of 5-aza and combined castration + 5-aza on preexisting prostate cancer in an animal model. Based on these preclinical findings, we suggest that 5-aza treatment may prolong the time to an androgen-independent status and thus survival in a hormone-deprived setting in prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / surgery
  • Animals
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / therapeutic use
  • Castration
  • Combined Modality Therapy
  • Decitabine
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Transgenic
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / surgery


  • Antimetabolites, Antineoplastic
  • Decitabine
  • Azacitidine