[Effect of epidermal growth factor receptor-selective tyrosine kinase inhibitor ZD1839 on nasopharyngeal carcinoma cells].
OBJECTIVE
ZD1839, an anilinoquinazoline, is an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which has been approved for the treatment of advanced non-small cell lung cancer by FDA. Nasopharyngeal carcinoma is of epithelial origin with overexpression of epidermal growth factor receptor and it remains unclear whether ZD1839 is useful in the treatment of nasopharyngeal carcinoma. The present study was designed to evaluate the effect of ZD1839 on nasopharyngeal carcinoma cell lines.


METHODS
The effect of ZD1839 on nasopharyngeal carcinoma cells (CNE1, CNE2, SUNE1) was determined by MTT assay. The effect of ZD1839 combined with cisplatin (DDP) or 5-fluouracil (5-FU) on nasopharyngeal carcinoma cell CNE2 was also evaluated. Burgi formula was adopted to analyze combination effect. The distribution of cell cycle and cell apoptosis rate were analyzed by flow cytometry.


RESULTS
The proliferation of nasopharyngeal carcinoma cell lines CNE1, CNE2, and SUNE1 was inhibited by ZD1839, and the effect was dose-dependent. The value of IC50 for the effect of ZD1839 on nasopharyngeal carcinoma cell lines CNE1, CNE2, and SUNE1 was 3.9 micromol/L, 5.6 micromol/L, and 5.5 micromol/L, respectively. ZD1839 could enhance the effect of DDP and 5-FU on CNE2 cells. The Q values by Burgi formula were 1.19+/-0.02 and 1.12+/-0.10, respectively. When CNE2 cells were treated with ZD1839 at the concentration of 0, 1.95, 3.9, 7.8, 15.6, 31.25 micromol/L, the percentages of G(0)/G(1) phase were (46.8+/-1.7)%, (48.8+/-1.6)%, (51.3+/-1.3)%, (54.0+/-1.3)%, (61.5+/-2.2)%, and (71.2+/-1.4)%, respectively; the percentages of S phase were (37.5+/-1.3)%, (35.8+/-1.6)%, (31.8+/-2.1)%, (34.3+/-2.7)%, (27.2+/-2.9)%, and (27.6+/-2.4)%, respectively;the percentages of G(2)/M phase were (15.7+/-0.4)%, (15.3+/-0.1)%, (16.9+/-0.9)%, (11.7+/-1.4)%, (11.3+/-0.7)%, and (1.1+/-0.8)%, respectively. When CNE2 cells were treated with ZD1839 at the concentration of 0, 1.95, 3.9, 7.8, 15.6, 31.25, 62.5 micromol/L, the rates of CNE2 cell apoptosis were (1.6+/-0.3)%, (1.7+/-0.3)%, (2.3+/-0.4)%, (3.3+/-0.4)%, (3.9+/-0.8)%,(8.0+/-1.1)%,and(14.3+/-2.3)%, respectively.


CONCLUSIONS
ZD1839 inhibits the proliferation of nasopharyngeal carcinoma cells and enhances the effect of cytotoxic drugs.ZD1839 induces CNE2 cell cycle arrest in the G1 phase and higher concentration of ZD1839 could induce apoptosis.
Wang
Shu-Sen
SS
Department of Internal Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, PR China.
Guan
Zhong-Zhen
ZZ
Jiang
Wen-Qi
WQ
Lin
Tong-Yu
TY
Zhang
Li
L
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005472:Fluorouracil / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D000077156:Gefitinib; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D002945:Cisplatin; D000077156:Gefitinib; D005472:Fluorouracil