丝裂原活化蛋白激酶磷酸酶1与胰腺癌细胞获得性耐药的关系  

Down regulation of mitogen activated protein kinase phosphatase-1 mediate acquired multidrug resistance in pancreatic adenocarcinoma cell line SW1990/Fu

作　　者：郭俊超[1] 赵玉沛[1] 廖泉[1] 陈革[1] 朱预[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院基本外科,100730

出　　处：《中华外科杂志》2006年第7期473-475,共3页Chinese Journal of Surgery

基　　金：国家自然科学基金资助项目(30371389)

摘　　要：目的探讨丝裂原活化蛋白激酶(MAPK)磷酸酶1(MKP-1)在介导胰腺癌耐药细胞株SW 1990/Fu产生获得性耐药过程中的可能机制。方法采用Northern印迹杂交和W estern蛋白免疫印迹杂交方法,检测MKP-1在体外诱导建立的人胰腺癌耐药细胞株SW 1990/Fu、亲本细胞株SW 1990和胰腺癌细胞株M iaPaCa-2中的表达,分析MKP-1在SW 1990/Fu产生获得性耐药前后的变化。结果Northern印迹杂交结果显示,在SW 1990/Fu、SW 1990和M iaPaCa-2细胞株中均检测到2400 bp的MKP-1 mRNA,MKP-1在SW 1990/Fu的表达水平明显低于SW 1990和M iaPaCa-2。在蛋白水平上,W estern蛋白免疫印迹杂交结果也表明,与SW 1990和M iaPaCa-2相比,MKP-1蛋白在SW 1990/Fu细胞中的表达水平明显降低。结论MAPK家族的关键调节酶MKP-1可能参与SW 1990/Fu获得性耐药的产生,推测细胞信号转导系统的改变可能是导致胰腺癌细胞产生获得性耐药的机制之一。Objective To investigate the role of mitogen activated protein kinase phosphatase-1 （MKP-1） in mediating acquired muhidrug resistanee in pancreatic adenocareinoma cell line SW1990/Fu. Methods To detect MKP-1 mRNA expression, Northern blot analysis was carried out in well established drug resistant panereatie adenoeareinoma cell line SW1990/Fu, SW1990 and MiaPaCa-2 eell lines. To further elucidate the exact role of MKP-1, Western blot hybridization was performed in these three cell lines. Results Northern blot analysis of total RNA isolated from SW1990/Fu, SW1990 and MiaPaCa-2 cell lines revealed the presence of the 2400 bp MKP-1 transcript7 at relatively high levels in pancreatic cancer cell lines SW1990 and MiaPaCa-2. In the SWI990/Fu, the MKP-1 transcript was detectable at very low level. Densitometrie analysis with normalization to 7S indicated that MKP-1 mRNA expression level was signifieandy decreased in SW1990/Fu in comparison with the parental and MiaPaCa-2 cell lines. MKP-1 protein expression level in SW1990/Fu detected by Western blot was coincident with mRNA level. Conclusions MKP-1 may be involved in acquired multidrug resistance in pancreatic adenoeareinoma, and we could hypothesized that alterations of intra-eellular transduetion signal system acts as an important role in muhidrug resistance of tumor cells.

关 键 词：胰腺肿瘤 抗药性 丝裂原活化蛋白激酶 

分 类 号：R735.9[医药卫生—肿瘤]