γ分泌酶抑制剂对非小细胞肺癌常用化疗药物敏感性的影响  

The affection of Gamma secretase inhibitors on chemotherapy drug sensitivity for non-small cell lung cancer

作　　者：何凤莲[1] 杜婷[2] 江倩[2] 张妍蓓[2] HE Feng-lian(Department of respiratory medicine,second affiliated hospital of Anhui University,Hefei,Anhui,230601,China)

机构地区：[1]安徽医科大学第二附属医院呼吸内科,安徽230601 [2]安徽医科大学第一附属医院老年呼吸内科,安徽230022

出　　处：《齐齐哈尔医学院学报》2018年第4期390-393,共4页Journal of Qiqihar Medical University

基　　金：安徽省教育厅重点项目(No.KJ2011A178;No.KJ2015A164);安徽省科技厅自然基金重点项目(No.1208085MH146);安徽省15年第一批科技攻关项目(No.1501041144)

摘　　要：目的探讨γ分泌酶抑制剂(DAPT)对非小细胞肺癌常用化疗药物紫杉醇、吉西他滨化疗敏感性的影响以及可能的作用机制。方法通过两种化疗药物分别诱导A549和H1299耐药株的产生,运用Western blot方法检测两种耐药细胞株中Notch3蛋白的表达。四甲基偶氮唑蓝(MTT)比色法检测紫杉醇和吉西他滨对两种肿瘤细胞的抑制效应,同时检测两种化疗药物联合γ分泌酶抑制剂(DAPT)后对肿瘤细胞抑制效应的影响。结果两种耐药的细胞株中Notch3蛋白的表达均明显升高;紫杉醇和吉西他滨对两种肿瘤细胞的活性均存在不同程度的抑制作用,联合DAPT后提高了紫杉醇和吉西他滨对两种肿瘤细胞增殖的抑制作用。结论γ分泌酶抑制剂提高紫杉醇和吉西他滨对非小细胞肺癌的敏感性,Notch3蛋白的表达与化疗药物抵抗相关,并且通过抑制Notch3通路可能提高化疗药物的敏感性。Objective This study explored the effect of Gamma secretase inhibitors（DAPT） on the sensitivity of paclitaxel and gemcitabine,and its possible mechanism.Methods The A549 and H1299 resistant strains were respectively induced by paclitaxel and gemcitabine.Western blot method was used to detect the expression of Notch3 protein.MTT method was used to detect the inhibition of paclitaxel and gemcitabine on nonsmall cell cancer（NSCLC） and detect the effect of Gamma secretase inhibitors combined the two drugs respectively on NSCLC.Results The expression of Notch3 protein was significantly increased in the two resistant strains.Paclitaxel and gemcitabine inhibited the activity of both tumor cells to varying degrees,and the combination of DAPT increased the inhibitory effect of paclitaxel and gemcitabine on the proliferation of the two kinds of tumor cells.Conclusions Gamma secretase inhibitors increased the sensitivity of paclitaxel and gemcitabine to NSCLC,Notch3 protein expression associated with chemotherapy resistant and inhibiting the Notch3 pathways may improve the sensitivity of chemotherapy drugs.

关 键 词：非小细胞肺癌 吉西他滨 紫杉醇 NOTCH3 

分 类 号：R734[医药卫生—肿瘤]