吉非替尼和依维莫司对EGFR-TKI耐药鼻咽癌细胞的作用

发布时间：2018-06-15 01:42

本文选题：吉非替尼 + 依维莫司　；参考：《医药导报》2014年01期

【摘要】：目的探讨吉非替尼和依维莫司对吉非替尼耐药鼻咽癌细胞的作用效果及分子作用机制。方法吉非替尼、依维莫司单独或联合作用人鼻咽癌细胞株HONE1后,采用噻唑蓝(MTT)法检测细胞的增殖抑制,流式细胞术检测细胞凋亡率及周期分布,Western blot检测细胞磷酸化丝氨酸苏氨酸蛋白激酶(p-AKT)、磷酸化核糖体S6蛋白激酶(pS6K)的表达水平。结果吉非替尼和依维莫司均呈浓度依赖性抑制HONE1细胞增殖,吉非替尼的半数抑制浓度(IC50)为17.92μmol·L-1,依维莫司的IC50为2.46 nmol·L-1,但二者联合作用效果与单药相比并未表现出明显的优势(P0.05);吉非替尼对p-AKT抑制作用不明显,依维莫司可下调p-S6K的表达,同时上调了p-AKT的表达,联合用药对pS6K和p-AKT表达的抑制作用并不明显强于单药。结论吉非替尼和依维莫司联合作用于吉非替尼耐药鼻咽癌细胞株HONE1没有表现出协同效应,表皮生长因子受体/丝氨酸苏氨酸蛋白激酶(EGFR/AKT)信号通路与雷帕霉素蛋白(mTOR)信号通路在鼻咽癌细胞中的关系有待进一步研究。
[Abstract]:Objective to investigate the effect and molecular mechanism of gefitinib and ivermostr on gifetini resistant nasopharyngeal carcinoma cells. Methods the proliferation inhibition of human nasopharyngeal carcinoma cell line HONE1 was detected by thiazolyl methoate (MTT) assay. Apoptosis rate and cell cycle distribution were detected by flow cytometry. The expression of phosphorylated serine threonine protein kinase (P-AKTK) and phosphorylated ribosomal S6 protein kinase (pS6K) were detected by Western blot. Results both gefitinib and ivermostatin inhibited the proliferation of HONE1 cells in a concentration-dependent manner. The IC50 of gefitinib was 17.92 渭 mol / L ~ (-1), the IC50 of ivermostr was 2.46 nmol / L ~ (-1), but the combined effect of the two drugs had no obvious advantage over the single drug (P0.05N), the inhibitory effect of gefitinib on p-AKT was not obvious, and the expression of p-S6K could be down-regulated by Evimostr. At the same time, the expression of p-AKT was upregulated, and the inhibitory effect of combined drug on pS6K and p-AKT expression was not significantly stronger than that of single drug. Conclusion the combination of gefitinib and ivermostatin has no synergistic effect on gemfelitini-resistant nasopharyngeal carcinoma cell line HONE1. The relationship between epidermal growth factor receptor / serine threonine protein kinase (EGFR / AKT) signaling pathway and rapamycin protein mTOR-signaling pathway in nasopharyngeal carcinoma cells needs further study.
【作者单位】：湖北省襄阳市中心医院肿瘤科;华中科技大学同济医学院附属同济医院肿瘤科;
【基金】：吴阶平医学基金资助项目(320.6700.09065) 国家自然科学基金资助项目(81272491)
【分类号】：R739.63

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