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. 2003 Mar;129(3):165-74. doi: 10.1007/s00432-003-0420-3. Epub 2003 Mar 4.


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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Gefitinib
  • Humans
  • In Vitro Techniques
  • Male
  • Phosphorylation
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinazolines / pharmacology*
  • Tumor Cells, Cultured
  • Tyrosine


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Quinazolines
  • Tyrosine
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Gefitinib