LB100对EGFR基因突变的肺腺癌细胞吉非替尼获得性耐药的逆转作用  

LB100 reverses the acquired resistance to gefitinib in lung adenocarcinoma cells with EGFR mutation

作　　者：单姗[1] 王艺朵 任涛[1] 

机构地区：[1]同济大学附属东方医院呼吸内科,上海200123 [2]复旦大学附属华山医院病理科

出　　处：《中华医学杂志》2016年第42期3398-3402,共5页National Medical Journal of China

基　　金：国家自然科学基金（81372347）;上海市优秀学术带头人计划（16XD1403100）

摘　　要：目的探讨蛋白质磷酸酶2A（PP2A）活性抑制剂LB100对表皮生长因子受体（EGFR）基因突变的肺腺癌细胞吉非替尼获得性耐药的逆转作用。方法以吉非替尼耐药细胞系NCI-1975及自行建立的吉非替尼耐药原代细胞株44-1为对象，通过基因测序法确定两种细胞EGFR基因突变类型；以吉非替尼分别单独或联合LB100处理两种细胞，通过细胞计数,8试剂盒（CCK8）计算不同用药组的半数抑制浓度（IC50）值，比较吉非替尼联合LB100后NCI-1975和44．1细胞对吉非替尼敏感性的变化；建立裸鼠移植瘤模型，通过比较各药物处理组移植瘤体积，观测联合LB100后吉非替尼对肿瘤生长抑制的变化。结果44-1及NCI—H1975细胞均携带EGFR基因敏感性L858R突变及耐药性T790M突变；44-1及NCI-1975细胞均显示对吉非替尼耐药性，IC50值分别为23．0、16．7μmol／L；联合LB100后，IC50值分别降至6．9、3．4μmol／L；裸鼠NCI-1975移植瘤实验中，LB100明显提高了吉非替尼对肿瘤生长的抑制能力（P〈0．05）。结论LB100可在一定程度上逆转肺腺癌细胞对吉非替尼的耐药性。Objective To investigate the possibility of the Protein Phosphatase 2A （PP2A） inhibitor, LB100, in reversing acquired resistance to gefitinib in lung adenocarcinoma with epidermal growth factor receptor （EGFR） gene mutation. Methods Cell line NCI-H1975 and established primary culture cell line 44-1 with gefitinib resistance were sequenced to determine the mutation type of EGFR gene. Cells were treated with gefitinib alone or combined with LB100 to determine the half maximal inhibitory concentration （IC50）, and sensitivity of 44 -1 and NCI-1975 to gefitinib alone or combined with LB100 was compared. The volume of NCI-H1975 xenografts with different drug treatments was observed to determine the efficiency of gefitinib with or without LB100 in tumor growth inhibition. Results Both 44 - 1 and NCI-1975 cells had double EGFR mutation （sensitive L858R mutation and resistant T790M mutation）. Both cells showed significant gefitinib resistance （ IC50 ： 23.0 μmol/L in 44 - 1, 16. 7 μmol/L in NCI-1975）. When combined with LB100, IC50 of gefitinib decreased to 6. 9 μmol/L in 44 - 1 cell and decreased to 3.4 μmol/L in NCI- H1975 cells. In NCI-1975 xenografts experiments, LB100 enhanced the ability of gefitinib in tumor growth inhibition （P 〈 0. 05 ）. Conclusion LB100 reverses acquired resistance to gefitinib in lung adenocarcinoma cell lines.

关 键 词：肺肿瘤 受体 表皮生长因子 抗药性 肿瘤 磷蛋白磷酸酶 吉非替尼 

分 类 号：R734.2[医药卫生—肿瘤]