LRP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的化疗耐药性和参与介导多药耐药的相关基因LRP和蛋白的表达,对比分析非小细胞肺癌的多药耐药性与LRP的关系。方法应用肿瘤细胞体外培养和MTT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LRP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,其耐药性与组织学类型和分化程度无关(P>0.05)。LRP在91例非小细胞肺癌中总的阳性表达率为53.8%鳞癌和腺癌相比LRP的表达无显著性差异(P>0.05)。且LRP的表达与三种化疗用药的耐药性均呈显著正相关(P<0.05),并且不同表达程度间也有显著差异性(P<0.05)。结论LRP在非小细胞肺癌中均有较高的阳性表达并参与介导了非小细胞肺癌固有多药耐药机制。

The Study of the Effect of LRP in 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) we explore the relation between chemoresistance and the expression of lung resistance-related protein gene(LRP)in NSCLC,and define the function of the gene in MDR mechanisms.Methods 91 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 three kinds of gene above was examined with immunohistochemical assay.Results 1.The percentage of drug resistance of cyclophamide,adriamycin and capsulation fluorouracil were 58.2%,56.0% and 46.2%,respectively.There are 27 cases resisting all three medications,while there are 19 cases sensitizing all three medications.The multidrug resistance was not associated with histological types and degree of differentiation of NSCLC.2.The expression percentage of LRP in NSCLC was 53.8%.There is not significant difference in the expression of LRP between human adeoncarcinoma and sequamous cell carcinoma(P>0.05).3.The correlation between the positive expression of LRP and the degrees of chemoresistance to the three kinds of agents was significant (P<0.05),and the degree of chemoresistance to the three kinds of agents among the different degrees of expressions of LRP are significantly different (P<0.05).Conclusions There are certain degrees of intrinsic resistance in different kinds of chemotherapeutic agents in NSCLC and the intrinsic multidrug resistance mechanisms may be of the co-effect of LRP.