Inhibitors of epidermoid growth factor receptor suppress cell growth and enhance chemosensitivity of nasopharyngeal cancer cells in vitro.
OBJECTIVE
Epidermoid growth factor receptor (EGFR, HER1) is overexpressed in a majority of head-and-neck cancers, including nasopharyngeal carcinoma (NPC). Although EGFR inhibitors appear to be effective for some head-and-neck cancers, their efficacy in NPC remains unclear.


METHODS
The effect of EGFR-specific tyrosine kinase inhibitors, including PD153035 and ZD1839, were studied in NPC-TW01, NPC-TW04, and HONE1 cell lines. The effect of combining EGFR inhibitors with cytotoxic agents was evaluated in NPC-TW04 cells.


RESULTS
All three NPC cell lines expressed EGFR. PD153035 and ZD1839 inhibited the growth of NPC cells with IC50s around 10 and 20 microM, respectively. These inhibitors, however, effectively suppressed ligand-stimulated EGFR activation in NPC cells with a much lower concentration (> or =0.1 microM). The growth-suppression activity of EGFR inhibitors was closely associated with suppression of AKT phosphorylation. LY294002, a phosphatidylinositol-3 kinase (P13K)/AKT inhibitor, did suppress the growth of NPC cells. Pretreatment of EGFR inhibitors by 24 h significantly enhanced the cytotoxic effect of doxorubicin, paclitaxel, cisplatin, and 5-fluororuacil in NPC-TW04 cells.


CONCLUSIONS
Our data indicate that inhibition of EGFR activation is not sufficient to induce growth inhibition in NPC cells in vitro. EGFR inhibitors may be useful adjuncts in treating NPC when combined with conventional anticancer drugs.
Hsu
Chih-Hung
CH
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Gao
Ming
M
Chen
Chi-Long
CL
Yeh
Pei-Yen
PY
Cheng
Ann-Lii
AL
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D014407:Tumor Cells, Cultured
D002945:Cisplatin; D004317:Doxorubicin; D066246:ErbB Receptors; D005472:Fluorouracil; D017239:Paclitaxel; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human