[Effect of epidermal growth factor receptor-selective tyrosine kinase inhibitor gefitinib on nasopharyngeal carcinoma xenografts]

Abstract

Background & objective: Gefitinib,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. We have found that the proliferation of nasopharyngeal carcinoma (NPC) cell lines CNE1,CNE2,and SUNE1 was inhibited by Gefitinib. The present study was designed to evaluate the effect of Gefitinib alone or in combination with cisplatin (DDP) on NPC CNE2 xenografts.

Methods: Exponentially growing CNE2 cells were prepared into cell suspension (1 x 10(7) cells/ml). Suspension of 200 mul of CNE2 cells was injected s.c. into the right flank area of the mice. After 7 days,when well-established tumors of 100-200 mm(3) were detected,mice were randomized into five groups: control group,Gefitinib (100 mg/kg) group,Gefitinib (200 mg/kg) group,DDP group,and Gefitinib (100 mg/kg) plus DDP group. Gefitinib was administered by oral gavage on days 1-5 of each week for 4 weeks. DDP was administered i.p. once a week for 4 weeks. Tumor volume was determined by direct measurement with caliper and calculated by the formula 1/2x(large diameter)x(small diameter)(2). The mice were sacrificed at two days after the treatment ended; tumor masses were removed and weighed. The tumor inhibition rates were calculated. The student's test was used to evaluated the statistical significance of the results.

Results: Growth curves showed that tumor masses of control group grew more rapidly than ones of every treatment group. The average tumor volume was significantly smaller in Gefitinib (200 mg/kg) group than in control group (P=0.02). The average tumor volume had no significant difference between Gefitinib (100 mg/kg) group and control group. The average tumor volume of DDP or Gefitinib (100 mg/kg) plus DDP group was smaller than that of control group(P=0.007 and 0.001,respectively). The average tumor volume had no significant difference between DDP and Gefitinib (100 mg/kg) in combination with DDP group. The tumor inhibition rates of Gefitinib (100 mg/kg) group,Gefitinib (200 mg/kg) group,DDP group,and Gefitinib (100 mg/kg) plus DDP group were 26.3%, 30.6%, 45.7% and 54.8%,respectively. The average tumor weight after treatment had no significant difference between Gefitinib (100 mg/kg) group and control group. The average tumor weights of Gefitinib (200 mg/kg) group,DDP group,Gefitinib (100 mg/kg) plus DDP group were all smaller than that of control group. The average tumor weight had no significant difference between DDP group and Gefitinib (100 mg/kg) plus DDP group.

Conclusion: Gefitinib could inhibit the growth of NPC CNE2 xenografts. Gefitinib in combination with DDP did not significantly potentiate the effect of DDP on NPC CNE2 xenografts.