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Bicalutamide demonstrates biologic effectiveness in prostate cancer cell lines and tumor primary cultures irrespective of Her2/neu expression levels.

Abstract：

OBJECTIVES:To evaluate the role of Her2/neu as a molecular marker predictive of the treatment response to bicalutamide in prostate cancer (PCa). METHODS:Four PCa cell lines with graded Her2/neu expression levels and 63 primary tumor cultures derived from men with PCa and selected according to Her2/neu 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 Her2/nue expression and drug efficacy was used to define the role of Her2/neu 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 Her2/neu levels (r = 0.053, P = .823). In primary cultures with high Her2/neu 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 Her2/neu 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 Her2/neu levels (r = 0.33, P = .101). CONCLUSIONS:Our biologic data seem to indicate that the antitumor effect of bicalutamide is independent of Her2/neu levels in preclinical models of PCa. Bicalutamide could be configured as a pharmacologic option to treat patients with high or low levels of Her2/neu.

journal_name

Urology

journal_title

Urology

authors

Gravina GL,Festuccia C,Millimaggi D,Tombolini V,Dolo V,Vicentini C,Bologna M

doi

10.1016/j.urology.2009.01.018

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

452-7

issue

eissn

0090-4295

issn

1527-9995

pii

S0090-4295(09)00091-0

journal_volume

pub_type

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Bicalutamide demonstrates biologic effectiveness in prostate cancer cell lines and tumor primary cultures irrespective of Her2/neu expression levels.