目前发现多个p38MAPK抑制剂能够增强肿瘤对化疗药物的敏感性,但机制尚不明确。因此我们选取了已进入Ⅲ期临床试验的新一代p38抑制剂BIRB796作为研究对象,探讨它是否能后逆转ABC转运蛋白介导的MDR。方法：MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT)法检测细胞毒实验；流式细胞仪检测阿霉素、罗{Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|selleck Anti-infection Compound Library|selleck Antiinfection Compound Library|selleck Anti-infection Compound Library|selleck Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|buy Anti-infection Compound Library|Anti-infection Compound Library半抑制浓度|Anti-infection Compound Library价格|Anti-infection Compound Library花费|Anti-infection Compound Library溶解度|Anti-infection Compound Library购买|Anti-infection Compound Library制造商|Anti-infection Compound Library查找购买|Anti-infection Compound Library订单|Anti-infection Compound Library mouse|Anti-infection Compound Library chemical structure|Anti-infection Compound Library分子量|Anti-infection Compound Library molecular weight|Anti-infection Compound Library数据表|Anti-infection Compound Library supplier|Anti-infection Compound Library体外|Anti-infection Compound Library细胞系|Anti-infection Compound Library concentration|Anti-infection Compound Library nmr|Anti-infection Compound Library体内|Anti-infection Compound Library clinical trial|Anti-infection Compound Library cell assay|Anti-infection Compound Library screening|Anti-infection Compound Library high throughput|buy Antiinfection Compound Library|Antiinfection Compound Library半抑制浓度|Antiinfection Compound Library价格|Antiinfection Compound Library花费|Antiinfection Compound Library溶解度|Antiinfection Compound Library购买|Antiinfection Compound Library制造商|Antiinfection Compound Library查找购买|Antiinfection Compound Library订单|Antiinfection Compound Library chemical structure|Antiinfection Compound Library数据表|Antiinfection Compound Library supplier|Antiinfection Compound Library体外|Antiinfection Compound Library细胞系|Antiinfection Compound Library concentration|Antiinfection Compound Library clinical trial|Antiinfection Compound Library cell assay|Antiinfection Compound Library screening|Antiinfection Compound Library high throughput|Anti-infection Compound high throughput screening|丹明123在细胞内的积累；以KBV200细胞建立裸鼠移植瘤模型探讨BIRB796体内逆转活性；蛋白测定用Western blotting法;ABCB1在mRNA表达水平用PCR和RT-PCR法测定；ATPase试剂盒测定BIRB796对ABCB1ATPase活性的影响；瞬时干扰RNA法观察沉默p38后,用MTT法检测紫杉醇对KBV200细胞的细胞毒性；Docking实不验模拟BIRB796与ABCB1的结合位点。结果：本研究通过MTT法证实了p38MAPK抑制剂BIRB796能够特异性的逆转ABCB1所介导MDR,但对ABCG2和ABCC1介导MDR却无逆转作用。通过流式细胞仪检测证明了BIRB796是通过增加ABCB1的底物(罗丹明123和阿霉素)在细胞中的浓度来实现逆转效果的。我们利用高表达ABCB1的KBV200细胞建立MDR时间裸鼠移植瘤模型,进一步验证了BIRB796在裸鼠体内逆转效果。Western blot以及PCR/Real time PCR结果显示BIRB796不改变ABCB1在蛋白和mRNA水平的表达。通过Pgp-GloTM试剂盒检测ABCB1ATPase的活性实验证明了BIRB796是通过调节ABCB1的ATP水解酶的活性来从而抑制了ABCB1的外排功能。通过瞬时干扰p38MAPK,证明了p38信号通路对BIRB796逆转ABCB1介导MDR没有协同作用。