Topo-Ⅱ蛋白在非小细胞肺癌中表达与耐药性的关系

Expression of Topo-Ⅱ Protein in Non-small Cell Lung Cancer and Relation with Drug Resistance

目的:检测非小细胞肺癌中Topo-Ⅱ蛋白的表达,分析非小细胞肺癌的化疗耐药性与其表达的关系,探讨Topo-Ⅱ在介导非小细胞肺癌耐药中的作用。方法:应用MTT法对52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+紫杉醇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Topo-Ⅱ蛋白表达的检测,并将其表达情况与对应的化疗耐药性进行相关分析。结果:27例(51.92%)对环磷酰胺耐药,23例(44.23%)对阿霉素耐药,17例(32.69%)对顺铂+紫杉醇耐药。其中,11例(21.19%)对三种用药均敏感,14例(26.92%)对三种用药均耐药。52例NSCLC中Topo-Ⅱ阳性者32例(61.53%)。Topo-Ⅱ蛋白在鳞癌表达高于腺癌,差异显著(χ2=1.23,P<0.05);但在腺癌、鳞腺癌、大细胞癌间表达表达无差异(χ2=0.46,P>0.05)。Topo-蛋白在不同分化程度NSCLC组织中的表达无差异(χ2=0.58,P>0.05)。Topo-Ⅱ蛋白的表达与NSCLC的三种化疗用药方案耐药性均有关(P<0.05),且Topo-Ⅱ蛋白的表达程度与NSCLC耐药程度成反比(P<0.05)。结论:Topo-Ⅱ在NSCLC细胞中表达的数量减少和(或)活性减低,使肿瘤细胞对相关药物的敏感性降低导致耐药。

Objective：To investigate the chemoresistance of non-small cell lung cancer （NSCLC） and the expres-sion of Topo-Ⅱ protein which can lead to multidrug resistance（MDR） we explore the relation between chmoresistance and the expression of Topo-Ⅱ in NSCLC. Method：52 cases of NSCLC were tasted with MTT assay to evaluate their chemoresistance. The chemotherapy drugs included cyclophamide adriamycin and cisplatin＋ paclitaxel. The expression of Topo-Ⅱ protein was examined with immunohistochemical assay. Result ：The percentage of drug resistance of paclitax-el ,adriamycin and cisplatin＋ fluorouracil were 51.92% ,44.23% and 32.69% ,respectively. There were 14 cases resist- ing all three medications, while there were 11 cases sensitizing all three medications. The expression percentage of Topo- protein in NSCLC was 61.53% ,and the expression was not associated with histological types and degree of differenti- ation of NSCLC（P〉0.05）,the degree of resistance had been increased with the degree decreased of Topo-Ⅱ expression （P〈0.05）. Conclusions ：The intrinsic multidrug resistance mechanisms may be caused by Topo-Ⅱ protein in NSCLC.