Background: The role of apoptosis in the regression of human prostate cancer after androgen deprivation therapy remains controversial. Detection of caspase-3, an ubiquitous effector of apoptosis, is a highly specific technique for in vivo evaluation of apoptosis.
Methods: Apoptotic rates were evaluated in the androgen-dependent CWR22 human prostate cancer xenograft in tumors that represented time points throughout the progression from androgen-stimulated to recurrent prostate cancer. Caspase-3 levels in formalin-fixed, paraffin-embedded specimens were quantified using immunohistochemical detection and video image analysis. Western blot analysis was used to confirm the results of immunodetection.
Results: Expression of caspase-3 reached a maximum on day 2 after castration, decreased on day 6, and remained low until tumor recurrence. The percentage of tumor area expressing caspase-3 increased from 2.51 +/- 0.44% in tumors from intact mice to 20.84 +/- 1.75% on day 2 after castration. Among immunopositive cells, the intensity of caspase-3 expression measured using the mean optical density (MOD) increased 45% (0.3762 +/- 0.003 to 0.5461 +/- 0.001) on day 2 after castration compared to levels detected in tumors from intact mice.
Conclusions: Apoptosis contributes to tumor regression after castration in the CWR22 human prostate cancer xenograft model.
Copyright 2003 Wiley-Liss, Inc.