Bicalutamide demonstrates biologic effectiveness in prostate cancer cell lines and tumor primary cultures irrespective of Her2eu expression levels.

摘要

OBJECTIVES: To evaluate the role of Her2eu as a molecular marker predictive of the treatment response to bicalutamide in prostate cancer (PCa). METHODS: Four PCa cell lines with graded Her2eu expression levels and 63 primary tumor cultures derived from men with PCa and selected according to Her2eu tumor levels were used. Primary tumor cultures and PCa cell lines were treated with bicalutamide (0.1-10 microM) in the presence of dehydrotestosterone (10(-12) M) for 4 days. The presence of a significant correlation between Her2ue expression and drug efficacy was used to define the role of Her2eu as molecular predictor of bicalutamide effectiveness. As an indicator of drug effectiveness we used the concentration that inhibits 50% values determined after bicalutamide treatment. RESULTS: After bicalutamide treatment, no significant differences in the concentration that inhibits 50% were found among the different tumor cell lines (P = .081). In this experimental model, the correlation analysis suggested that the effectiveness of this drug was not influenced by Her2eu levels (r = 0.053, P = .823). In primary cultures with high Her2eu levels (43 tumor cultures), the mean value of the concentration that inhibits 50% for bicalutamide was 0.43 +/- 0.13 microM, and in cultures with low Her2eu levels (20 tumor cultures), the same parameter was 0.5 +/- 0.16 microM (P = .14). The correlation analysis suggested that the effectiveness of this drug was not influenced by Her2eu levels (r = 0.33, P = .101). CONCLUSIONS: Our biologic data seem to indicate that the antitumor effect of bicalutamide is independent of Her2eu levels in preclinical models of PCa. Bicalutamide could be configured as a pharmacologic option to treat patients with high or low levels of Her2eu.