中文摘要：

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SWl990／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Western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SWl990／Fu、亲本细胞株SWl990和胰腺癌细胞株MiaPaCa-2中的表达，分析MKP-1在SW1990／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SWl990／Fu、SWl990和MiaPaCa~细胞株中均检测到2400bp的MKP-1mRNA，MKP-1在SWl990／Fu的表达水平明显低于SWl990和MiaPaCa-2。在蛋白水平上，Western蛋白免疫印迹杂交结果也表明，与SWl990和MiaPaCa4相比，MKP-1蛋白在SWl990／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SWl990／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。

英文摘要：

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.