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目的检测非小细胞肺癌(NSCLC)中Topo-II蛋白与p53蛋白的表达,分析NSCLC化学治疗耐药性与二者表达的关系,探讨Topo-II蛋白与p53蛋白在介导NSCLC耐药中的意义。方法应用单核细胞直接细胞毒性测定法对40例NSCLC组织进行体外药物敏感试验,观察对紫杉醇、阿霉素、顺铂+吉西他滨3种用药方案的耐药情况,并用免疫组织化学方法对其进行Topo-II蛋白和p53蛋白表达的检测,并将其表达情况与对应的化学治疗耐药性进行相关性分析。结果 21例(52.5%)对紫杉醇耐药,23例(57.5%)对阿霉素耐药,12例(30.0%)对顺铂+吉西他滨耐药。其中7例(17.5%)对3种用药均敏感,11例(27.5%)对3种用药均耐药。Topo-II蛋白和p53蛋白阳性表达与分化程度无关(P>0.05);Topo-II蛋白阳性表达与组织学类型无关(P>0.05),p53蛋白在腺癌中的阳性表达高于其他组织学类型(P<0.05);Topo-II蛋白表达与3种用药方案耐药性负相关(P<0.05);p53蛋白表达与3种用药方案耐药性正相关(P<0.05);NSCLC中p53蛋白表达与Topo-II蛋白表达正相关(P<0.05)。结论 Topo-II蛋白与p53蛋白均介导了NSCLC多药耐药。
Objective To detect the expression of Topo-II protein and p53 protein in non-small cell lung cancer (NSCLC), analyze the relationship between chemoresistance and the expression of chemoresistance in NSCLC, and to explore the relationship between Topo-II protein and p53 protein in mediating drug resistance of NSCLC significance. Methods 40 cases of non-small cell lung cancer (NSCLC) tissues were subjected to drug sensitivity test by monocyte direct cytotoxicity assay. The drug resistance of paclitaxel, doxorubicin, cisplatin and gemcitabine was observed. Immunohistochemistry Topo-II protein and p53 protein expression were detected, and their expression was correlated with the corresponding chemotherapeutic drug resistance. Results 21 (52.5%) were resistant to paclitaxel, 23 (57.5%) were resistant to doxorubicin and 12 (30.0%) were resistant to cisplatin + gemcitabine. Of these, 7 (17.5%) were sensitive to all 3 drugs and 11 (27.5%) were resistant to 3 drugs. The positive expression of Topo-II protein and p53 protein had no correlation with the degree of differentiation (P> 0.05). The positive expression of Topo-II protein was not related to histological type (P> 0.05), but the positive expression of p53 protein in adenocarcinoma was higher than other histological (P <0.05). The expression of Topo-II protein was negatively correlated with the drug resistance of the three drug regimens (P <0.05). The p53 protein expression was positively correlated with the drug resistance of the three drug regimens (P <0.05) Protein expression was positively correlated with Topo-II protein expression (P <0.05). Conclusion Both Topo-II protein and p53 protein mediate multidrug resistance in NSCLC.