Topo-Ⅱ蛋白与p53蛋白在非小细胞肺癌耐药性中的表达

摘要

Objective To detect the expressions of Topo-II protein and p53 protein in non-small cell lung cancer (NSCLC) .analyze the relationship between chemotherapy resistance of NSCLC and the expressions of these two proteins,and discuss the significance of mediation of resistance of NSCLC by Topo-II protein and p53 protein. Methods With mono-nuclear cell direct cytotoxicity assay method,drug sensitivity tests in vitro were taken on NSCLC tissues of 40 cases,drug resistances of three therapeutic regimens-paclitaxel.adriamycin and cisplatin plus gemcitabine were observed,the expressions of Topo-II protein and pS3 protein were detected by immunohistochemistry,and the correlations between the expressions and the corresponding chemotherapy resistance were analyzed. Results There were 21 cases(52. 5% ) resisting paclitaxel,23 cases(57. 5% ) resisting adriamycin,12 cases(30.0% ) resisting cisplatin plus gemcitabine. There were 11 cases(27. 5% ) resisting all the three medications,while 7 cases(17.5% ) were sensitive to all the three medications. The positive expressions of Topo-II protein and p53 protein were not associated with degree of differentiation in NSCLC(P>0.05). The positive expression of Topo-II protein was not associated with tissue types (P > 0.05) , the expression of p53 protein in adenocarcinoma was significantly higher than that in other tissue types( P < 0.05 ). The expression of Topo-II protein was inversely correlative with drug resistances of three therapeutic regimens( P < 0.05 ) , while the expression of p53 protein was positively related with drug resistances of three therapeutic regimens ( P < 0. 05). The expressions of p53 protein and Topo-II protein were positively correlated in NSCLC (P < 0.05 ). Conclusion Both Topo-II protein and p53 protein have mediated multidrug resistance of NSCLC.%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 Tropo-Ⅱ蛋白与p53蛋白均介导了NSCLC多药耐药.