舌鳞癌细胞对Iressa的敏感性及其表皮生长因子受体突变

Sensitivity of Tongue Squamous Cell Carcinoma to Iressa and Its EGFR Mutation

目的研究中国人舌鳞癌细胞系对表皮生长因子受体(EGFR)抑制剂Iressa的敏感性及其EGFR突变,初步探讨Iressa在头颈鳞癌治疗中的价值。方法以中国人舌鳞癌细胞系Tscca和Tca8113为研究对象,采用MTT法检测Iressa对其增殖的抑制作用;流式细胞仪检测细胞周期和凋亡;对Tscca和Tca8113进行EGFR外显子18～21测序。结果 Iressa对Tscca、Tca8113均有显著的增殖抑制作用,呈剂量依赖性。细胞周期分析显示,较低浓度Iressa(18.2μmol/L和36.4μmol/L)可使Tscca和Tca8113细胞G0/G1期比例增高;流式细胞仪分析显示高浓度Iressa可诱导Tscca和Tca8113细胞凋亡。测序发现Tscca和Tca8113的EGFR外显子20存在同一静止突变,即2361G-A,Q787Q。结论 Iressa可抑制Tscca和Tca8113的增殖,呈剂量依赖性;较低浓度时诱导细胞周期G0/G1期比例增高,高浓度时诱导凋亡,其抑制作用与EGFR突变未见相关性。

Objective To evaluate the effect of Iressa on squamous cell carcinoma lines Tca8113,Tscca of tongue and study the mutation statuses of EGFR gene in them.Methods The effect of Iressa on Tscca and Tca8113 cells was detected by MTT assay.The distribution of cell cycle and apoptosis rate were assayed by flow cytometry and Hoechst staining respectively.The sequence of EGFR exons 18-21 of the two cell lines was analyzed.Results The proliferation of Tscca and Tca8113 cells was inhibited by Iressa in a dose-dependent manner.The IC50 of Iressa on Tscca and Tca8113 cells was 18.03 and 29.98 μmol/L respectively.When Tscca and Tca8113 cells were treated by low concentrations of Iressa（18.2 and 36.4 μmol/L）,the percentage of cells in G0/G1 phase was increased and that in G2/M phase decreased significantly.The apoptosis rate was significantly increased when Tscca and Tca8113 cells were treated with high concentrations of Iressa（72.7 and 145.4 μmol/L）.The same silent point mutation in each cell line was found in the EGFR exon 20（2361G-A,Q787Q）.Conclusion Iressa can inhibit the proliferation of tongue squmous cell carcinoma lines in a dose-dependent manner.Low concentration of Iressa induces the increased percentage of G0/G1cells,and high concentration of Iressa induces apoptosis.There is no correlation between Iressa sensitivity and EGFR mutation.