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ABCG2和V-ATPase在非小细胞肺癌中的表达及与化疗药物耐药相关性研究
The Expression of ABCG2 and V-ATPase in Nsclc and Their Correlation with Drug-resistance
【作者】 刘博雅;
【作者基本信息】 第四军医大学 , 外科学, 2010, 硕士
【摘要】 目的:检测ABCG2和V-ATPase在非小细胞肺癌(NSCLC)组织中的表达,分析ABCG2和V-ATPase在NSCLC病理分类、TNM分期、病理分级中的表达差异性以及二者表达的相关性。分析二者表达与相应肿瘤组织对化疗药物耐药性的相关性。方法:收集临床NSCLC组织样本,采用免疫组化EnVinsion法和RT-PCR方法检测ABCG2和V-ATPase在NSCLC中的表达,采用MTT法检测细胞对化疗药物耐药性。用统计学软件分析ABCG2和V-ATPase表达的差异性和相关性,以及和耐药性的相关性。结果:ABCG2、V-ATPase在腺癌和鳞癌中有表达。二者在鳞癌、腺癌的表达均有差异。ABCG2在腺癌TNM分期中的表达差异性显著;在腺癌和鳞癌病理分级的表达差异性显著,P值分别为0.028、0.000。V-ATPase在腺癌TNM分期、鳞癌病理分级间的表达存在差异。在总体样本及腺癌、鳞癌中ABCG2和V-ATPase表达的相关性检验显示二者存在相关性(P<0.001)。腺癌的耐药性高于鳞癌。ABCG2和V-ATPase的表达量和样本对环磷酰胺、顺铂、卡铂的耐药性相关。结论:ABCG2的表达水平与腺癌的临床分期有关,和腺癌、鳞癌的恶性程度有关;V-ATPase的表达水平与腺癌的临床分期有关,与鳞癌恶性程度有关。ABCG2和V-ATPase的表达存在相关关系。V-ATPase和ABCG2可能共同参与NSCLC多药耐药的形成。
【Abstract】 OBJECTIVE:To determine the expressions of ABCG2 and V-ATPase in NSCLC and the expression correlation between ABCG2 and V-ATPase. To investigate the correlation between their expression rates and drug-resistance.METHODS:Expressions of ABCG2 and V-ATPase were accessed with EnVinsion immunohistochemistry and RT-PCR in tumor samples. Their drug resistance to cyclophosphamide, 5-FU, GEM, TAX, DDP, Doxorubicin, NVB, HCPT, CBP were evaluated by MTT assay. The corresponding data was analyzed statistically.RESULT:Expressions of ABCG2 and V-ATPase were found both in the lung adenocarcinoma and squamous cell lung cancer. ABCG2 is expressed significantly differently among TNM stages of lung adenocarcinoma as well as among pathological grades of lung adenocarcinoma (P=0.028) and squamous cell lung cancer (P=0.000). The level of V-ATPase expression was associated with TNM stages of lung adenocarcinoma and pathological grades of squamous cell lung cancer. Additionally, significant correlation was found between expression of ABCG2 and V-ATPase in all samples, adenocarcinoma and squamous cell cancer (P<0.001). In the MTT assay, it shows higher resistance level in the adenocarcinoma than in the squamous cell lung cancer. The correlation between the expression of ABCG2 and V-ATPase and the drug resistance level to cyclophosphamide, CBP and DDP is significant .CONCLUSION:The level of ABCG2 expression is associated with TNM stages of lung adenocarcinoma as well as the degree of the malignancy of both squamous cell lung cancer and lung adenocancinoma. The levels of V-ATPase expression were associated with TNM stages of lung adenocarcinoma and the degree of malignancy of squamous cell lung cancer. Significant correlation was found between expression of ABCG2 and V-ATPase, which indicated that they may co-work to participate the machanism of anticancer drug resistance.