Gefitinib (Iressa) potentiates the effect of ionizing radiation in thyroid cancer cell lines.
OBJECTIVE
To determine whether inactivation of epidermal growth factor receptor (EGFR) kinase activity will sensitize thyroid cancer cell lines to ionizing radiation-induced death.


METHODS
Established human thyroid cancer cells lines were studied.


METHODS
Colony formation assay was used to determine the effect of Gefitinib, a small molecule inhibitor of EGFR, on anaplastic (ARO) and follicular (WRO) thyroid cancer cell lines. In addition, colony formation assay was used to determine the effect of ionizing radiation in the presence or absence of Gefitinib. EGFR protein expression on the cell lines and inactivation of EGFR kinase by Gefitinib was analyzed by Western blot. Immunohistochemistry was performed on archived thyroid cancer tissue to demonstrate expression of EGFR.


RESULTS
Incubation with Gefitinib caused decreased phosphorylation of EGFR protein in established thyroid cancer cell lines as measured by Western blot. Inhibition of EGFR kinase activity by Gefitinib resulted in a dose-dependent decrease in colony formation in both ARO and WRO thyroid cancer cell lines. Addition of Gefitinib in combination with ionizing radiation reduced cell proliferation in ARO (P = .0084) and WRO (P = .0252) as measured by colony formation assay.


CONCLUSIONS
Inactivation of the EGFR kinase by Gefitinib potentiates the ionizing radiation-induced inhibition of cell proliferation in thyroid cancer cell lines. Use of this combination treatment of Gefitinib and ionizing radiation may be a promising therapy for anaplastic thyroid and metastatic follicular thyroid cancer and should be extended into animal models.
Lopez
Jay Patrick
JP
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, San Diego, California 92093, USA.
Wang-Rodriguez
Jessica
J
Chang
Catherine Y
CY
Sneh
Gabriel
G
Yu
Michael Andrew
MA
Pardo
Francisco S
FS
Aguilera
Joseph
J
Ongkeko
Weg M
WM
D018263:Adenocarcinoma, Follicular / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib