突变型p53与胃癌细胞多药耐药性关系的研究

目的：研究胃癌细胞中突变型p53和MDR-1基因的表达及其与不同化疗药物敏感性的关系。方法：将突变型p53、sv40Tag（封闭p53）导入胃癌细胞株SGC-7901中，研究胃癌细胞中MDR-1基因表达的变化；用MTT法比较各组细胞对化疗药的敏感性。结果：导入突变型p53细胞株的MDR-1基因mRNA表达比导入突变型p53＋sv40Tag细胞株、对照组MDR-1基因mRNA表达强；导入突变型P53细胞株对5-氟脲嘧啶（5-Fu）耐药性与导入突变型P53＋sv40Tag细胞株和对照组比较均有显著性差异（P〈0．05），而后两者之间耐药性差异无显著性（P〉0．05）；导入突变型p53细胞株和导入突变型p53＋sv40Tag细胞株对阿霉素（ADM）耐药性与对照组比较均有显著性差异（P〈0．05），而前两者之间对ADM的耐药性差异无显著性（P〉0．05）。导入突变型p53细胞株、导入突变型p53＋sv40Tag细胞株及对照组细胞株对顺铂（CDDP）耐药性均无显著性差异（P〉0．05）。结论：突变型p53能促进MDR-1 mRNA表达，与肿瘤细胞发生多药耐药密切相关。

Relation between mutant p53 and multidrug resistance in gastric cancer

Objective: To explore the relationship between mutant p53 and multidrug resistance in gastric cancer.Methods: Mutant p53(mp53) and mp53+sv40Tag were transferred to gastric cancer cell line SGC-7901.The MDR-1 mRNA was examined using RT-PCR,and the difference in chemotherapeutic sensitivity of SGC-7901 cells with mutant p53 was compared with those with mp53+sv40Tag and controls by MTT method.Results: SGC-7901 cells with mutant p53 showed higher MDR-1 mRNA than that of other two groups.SGC-7901 cells with mutant p53 showed higher chemotherapeutic sensitivity to 5-Fu than that with mp53+sv40Tag and control(P<0.05),but no difference between those with mp53+sv40Tag and control(P>0.05).SGC-7901 cells with mutant p53 and those with mp53+sv40Tag showed higher chemotherapeutic sensitivity to ADM than control(P<0.05),but no difference between those with mp53 and with mp53+sv40Tag(P>0.05).There was no difference in chemotherapeutic sensitivity of SGC-7901 cells with mutant p53 compared with those with mp53+sv40Tag and control to CDDP(P>0.05).Conclusion: Mutante p53 genes relates to multidrug resistance of gastric cancer.