Growth inhibition of nasopharyngeal carcinoma cells by EGF receptor tyrosine kinase inhibitors.
Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin occurring with a high incidence in southern China and southeast Asia. Radiotherapy is the main treatment modality for NPC. No effective chemotherapy is available. Since prevention of EGF/EGFR binding by an EGFR specific monoclonal antibody suppressed the growth of NPC xenografts, we examined potential anti-NPC activity by a group of specific inhibitors of the EGFR family of tyrosine kinases. We found that HONE-T1 NPC cells expressed high levels of EGFR tyrosine kinase activity upon stimulation by EGF. The receptor tyrosine kinase activity was specifically inhibited by either reversible (PD158780) or irreversible (PD168393) inhibitors specific for EGFR family tyrosine kinases. This inhibition led to a dose-dependent suppression of anchorage-independent growth as determined by soft agar assays. A structural analog (PD159805) with no inhibitory activity against EGFR tyrosine kinase had no effect on HONE-T1 cell growth in agar. Furthermore, growth of HONE-T1 xenografts in SCID mice was also inhibited by treatment with PD158780 and PD 168393. This data provides an appealing application of EGFR tyrosine kinase inhibitors for the treatment of nasopharyngeal carcinomas.
Sun
Y
Y
Department of Molecular Biology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA. yi.sun@wl.com
Fry
D W
DW
Vincent
P
P
Nelson
J M
JM
Elliott
W
W
Leopold
W R
WR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011743:Pyrimidines / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C107875:6-(methylamino)pyrido(3,4-d)pyrimidine; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors