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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

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Abstract

Purpose.

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.

Experimental design.

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 IC50s of 0.46–0.97 μM, and inhibited cellular proliferation with IC50s of 0.37–1.03 μM. 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 IC50 of 0.45 μM. At doses >1 μM, 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.

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Acknowledgments.

Dr. Adriano Angelucci was supported by a research fellowship by FIRC, Fondazione Italiana per la Ricerca sul Cancro, Milan, Italy. ALVA-31 cells were obtained via a collaborative arrangement with the Miami GRECC (Geriatric Research, Education and Clinical Center, Miami, Fla., USA). We thank Dr Demetrio Del Monaco, Senior Medical Adviser of AstraZeneca Italy (Basiglio, Milan, Italy) for his kind cooperation and scientific support. 'Iressa' and 'Casodex' are trademarks of the AstraZeneca group of companies.

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Authors and Affiliations

  1. Prostate Biology Laboratory, Department of Surgery, University of L'Aquila, Medical School, Coppito-2, 67100, L'Aquila, Italy

    Carlo Vicentini, Giovanni Luca Gravina & Angelo Marronaro

  2. Prostate Biology Laboratory, Department of Experimental Medicine, University of L'Aquila, Medical School, Coppito-2, L'Aquila, Italy

    Claudio Festuccia, Adriano Angelucci & Mauro Bologna

  3. Department of Basic and Applied Biology, University of L'Aquila, Science and Technology School, Coppito-2, L'Aquila, Italy

    Mauro Bologna

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  1. Carlo Vicentini
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  2. Claudio Festuccia
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  3. Giovanni Luca Gravina
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  4. Adriano Angelucci
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  5. Angelo Marronaro
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  6. Mauro Bologna
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Correspondence to Mauro Bologna.

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Vicentini, C., Festuccia, C., Gravina, G.L. et al. 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. J Cancer Res Clin Oncol 129, 165–174 (2003). https://doi.org/10.1007/s00432-003-0420-3

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  • DOI: https://doi.org/10.1007/s00432-003-0420-3

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