MRP的表达与非小细胞肺癌耐药性的关系

目的探讨非小细胞肺癌(NSCLC)的化疗耐药性和参与介导多药耐药的相关基因和蛋白(MRP)的表达,对比分析非小细胞肺癌的多药耐药性与三种耐药相关基因表达的关系。方法应用肿瘤细胞体外培养和药敏实验法对91例未经化疗的非小细胞肺癌进行体外化疗药物敏感性测试,观察非小细胞肺癌分别对环磷酰胺、阿霉素、顺铂 氟尿嘧啶三种单药和联合用药方案耐药情况和总的耐药情况,并用免疫组织化学方法对其进行MRP基因表达的检测,并将其表达情况与对应的化疗耐药性进行相关分析。结果91例NSCLC化疗敏感性检测结果显示:53例(58.2%)对环磷酰胺耐药,51例(56.0%)对阿霉素耐药,42例(46.2%)对顺铂 氟尿嘧啶耐药。其中,19例(20.9%)对三种用药均敏感,27例(29.8%)对三种用药均耐药,尚不能认为其耐药性与组织学类型和分化程度有关(P>0.05)。MRP在91例非小细胞肺癌中总的阳性表达率为73.6%。鳞癌和腺癌相比MRP的表达差异无统计学意义(P>0.05),而且MRP的表达与对三种化疗用药的耐药性均呈正相关(P<0.05),并且不同表达程度间差异也有统计学意义(P<0.05)。结论MRP在非小细胞肺癌中均有较高的阳性表达并共同介导参与了非小细胞肺癌固有的多药耐药机制。

The correlation between the expression of MRP and the mechanism of drug resistance of non - small cell lung cancer

Objective To investigate the chemoresistance of non-small cell lung cancer(NSCLC) and the expression of correlative protein and genes which can lead to multidrug resistance(MDR),and to explore the relation between chemoresistance and the expression of MRP in NSCLC,and define the function of the gene in MDR mechanisms.Methods Ninty-one cases of NSCLC were tested with MTT assay to evaluate their chemoresistance.The chemotherapy drugs include cyclophamide,adriamycin and cisplatin fluorouracil.The expression of the gene above was examined with immunohistochemical assay.Results 1.The percentage of drug resistance of cyclophamide,adriamycin and cisplatin fluorouracil were 58.2%,56.0% and 46.2%,respectively.There were 27 cases resisting all three medications,while there were 19 cases sensitizing all three medications.The multidrug resistance could not thought to be associated with histological types or degree of differentiation of NSCLC.2.The expression percentage of MRP in NSCLC was 73.6%.There was no significant difference in the expression of MRP between human adeoncarcinoma or sequamous cell carcinoma(P>(0.05)).3.The correlation between the positive expression of MRP and the degrees of chemoresistance to the three kinds of agents were significantly respectively(P<0.05),and among the degree of chemoresistance to the three kinds of agents the different degrees of expressions of MRP were significantly different(P<0.05).Conclusion The intrinsic multidrug resistance mechanisms may be of the effect of MRP gene.