Bicalutamide demonstrates biologic effectiveness in prostate cancer cell lines and tumor primary cultures irrespective of Her2/neu expression levels.
OBJECTIVE
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.
Gravina
Giovanni Luca
GL
Department of Experimental Medicine, University of L'Aquila, San Salvatore Hospital, Italy.
Festuccia
Claudio
C
Millimaggi
Danilo
D
Tombolini
Vincenzo
V
Dolo
Vincenza
V
Vicentini
Carlo
C
Bologna
Mauro
M
D000726:Androgen Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor; D009570:Nitriles; D017430:Prostate-Specific Antigen; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D014105:Tosyl Compounds; C053541:bicalutamide