Inhibition of transforming growth factor alpha (TGF-alpha)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868

Br J Cancer. 1999 Mar;79(7-8):1098-103. doi: 10.1038/sj.bjc.6690175.


The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01CDDP. Transforming growth factor alpha (TGF-alpha)-stimulated growth was completely inhibited by concentrations > or =0.3 microM in the PE01 and PE04 cell lines and by > or =0.1 microM in SKOV-3 cells. TGF-alpha inhibition of PE01CDDP growth was reversed by concentrations > or =0.1 microM ZM 252868. TGF-alpha-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations > or =0.3 microM, completely inhibited TGF-alpha-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 microM ZM 252868 in PE01, SKOV-3 and PE01CDDP cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.

MeSH terms

  • Cell Division / drug effects
  • Enzyme Inhibitors / pharmacology*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / drug effects*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / metabolism
  • Quinazolines / pharmacology*
  • Receptor, ErbB-2 / drug effects
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3
  • Signal Transduction
  • Transforming Growth Factor alpha / antagonists & inhibitors*
  • Transforming Growth Factor alpha / pharmacology
  • Tumor Cells, Cultured / drug effects


  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Quinazolines
  • Transforming Growth Factor alpha
  • ZM 252868
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3