Prostate cancer cell proliferation is strongly reduced by the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in vitro on human cell lines and primary cultures.
OBJECTIVE
To investigate the effects of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ZD1839 ('Iressa') on the cellular proliferation of androgen-sensitive and androgen-independent human prostatic cancer cell lines and primary cultures in vitro.


METHODS
In this study, we investigated the effects of the quinazoline ZD1839, a potent, selective EGFR-TKI, on the EGFR autophosphorylation and cellular proliferation of androgen-sensitive (ND1, LNCaP, and ALVA-31) and androgen-independent (PC3, DU145, and TSU-Pr1) human prostatic cancer cell lines and 20 primary cultures derived from human prostatic cancer tissue.


RESULTS
EGFR was present and phosphorylated in all cell lines tested. ZD1839 reduced EGFR autophosphorylation in intact cell lines with IC(50)s of 0.46-0.97 microM, and inhibited cellular proliferation with IC(50)s of 0.37-1.03 microM. Constitutive EGFR autophosphorylation was low in primary cell cultures, but addition of EGF (50 ng/ml) caused marked EGFR autophosphorylation; cellular proliferation in the presence of EGF was inhibited by ZD1839 with a mean IC(50) of 0.45 microM. At doses >1 microM, ZD1839 induced apoptosis in both androgen-dependent and androgen-independent PCa cell lines. CONCLUSION. Our experiments suggest that EGFR-TKIs such as ZD1839 may have potential in blocking the growth and progression of human prostatic cancers even in early phases of the disease.
Vicentini
Carlo
C
Prostate Biology Laboratory, Department of Surgery, University of L'Aquila, Medical School, Coppito-2, 67100, L'Aquila, Italy.
Festuccia
Claudio
C
Gravina
Giovanni Luca
GL
Angelucci
Adriano
A
Marronaro
Angelo
A
Bologna
Mauro
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D066246:ErbB Receptors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib