四甲基偶氮唑盐体外药物敏感试验联合多药耐药基因1检测预测非小细胞肺癌的化疗敏感性  

Predicting Clinical Chemosensitivity of Non-small Cell Lung Cancer Using Methylthiazal Assay Combined with Detection of Multidrug Resistance Gene 1

作　　者：尹迎春[1] 王新美[1] 王新云[1] 韩红梅[1] 侯震波[1] 张保华[1] 张日民[1] 

机构地区：[1]淄博市中心医院病理科,山东淄博255036

出　　处：《中国胸心血管外科临床杂志》2012年第5期547-550,共4页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

摘　　要：目的评价四甲基偶氮唑盐(MTT)药物敏感试验联合多药耐药基因1(MDR1)检测预测原发性非小细胞肺癌(NSCLC)的化疗敏感性,为临床个体化治疗提供依据。方法选择淄博市中心医院2009～2011年手术切除的80例NSCLC患者[男46例,女34例;中位年龄54(29～81)岁]的新鲜标本,采用MTT药物敏感试验检测患者对顺铂(DDP)、吉西他滨(GEM)、多西紫杉醇(DOC)、依托泊苷(VP-16)及长春瑞滨(NVB)的体外药物敏感性,采用实时荧光定量逆转录-聚合酶链反应(RT-PCR)技术检测肿瘤组织MDR1表达水平。结果经化疗药物作用后,体外培养的NSCLC细胞出现不同程度的形态学改变、代谢活性下降及凋亡。MTT法检测结果提示,不同个体NSCLC细胞对不同化疗药物的敏感性不同,NSCLC细胞对不同化疗药物敏感性亦不同:对DOC、GEM及VP-16的敏感性高于DDP和NVB(42.5%±9.5%、40.5%±6.5%、38.4%±7.6%vs.31.5%±8.5%、32.5%±7.8%,P<0.05)。肿瘤组织中MDR1的阳性表达率为40.0%(32/80),MDR1阳性表达与患者肿瘤组织学类型、分化程度、淋巴结转移情况及TNM分期无关(P>0.05)。MDR1阳性表达与NVB(χ2=5.209,P=0.022)、GEM(χ2=4.769,P=0.029)、VP-16(χ2=4.596,P=0.032)及DDP(χ2=6.086,P=0.014)的体外耐药相关,而与DOC的体外耐药不相关(χ2=0.430,P=0.512)。结论 MTT药物敏感试验可有效预测临床化疗药物敏感性,MTT药物敏感试验联合MDR1检测可提高预测NSCLC化疗敏感性,指导其个体化治疗。Objective To predict clinical chemotherapy sensitivity of primary non-small cell lung cancer（NSCLC） by methylthiazal（MTT） tumor chemosensitivity assay method in vitro and detection of multidrug resistance gene1（MDR1）,and provide reference for clinical individualized treatment.Methods We selected 80 fresh primary NSCLC samples from NSCLC patients who underwent surgical resection in Zibo Central Hospital Affiliated to Binzhou Medical College between January 2009 and December 2011.There were 46 male patients and 34 female patients with their median age of 54（29 to 81）years.Viable NSCLC cells obtained from malignant tissue were tested for their sensitivity to cisplatin（DDP）,gemcitabine（GEM）,docetaxe（DOC）,etoposide（VP-16）,and vinorelbine（NVB） using MTT assay in vitro.Fluorescent quantitative reverse transcriptase-polymerase chain reaction（RT-PCR） was used to analysis the expression level of multidrug resistance gene1（MDR1）.Results After exposure to antitumor drugs,morphologic changes,decrease of metabolic activity,and apoptosis were detected in NSCLC cells.MTT results showed that different individual cancer cells had different chemosensitivity to antitumor drugs,and cancer cells also had different chemosensitivity to different antitumor drugs.Inhibitory rates of cancer cells exposed to DOC,GEM,and VP-16 were significantly higher than those of cancer cells exposed to DDP and NVB（42.5%±9.5%,40.5%±6.5%,38.4%±7.6% versus 31.5%±8.5%,32.5%±7.8%,P0.05）. The positive rate of MDR1 in tumor tissues was 40.0%（32/80）.The expression of MDR1 was not associated with tumor histological type,degree of differentiation,lymph node metastasis and TNM stage.The expression of MDR1 was associated with resistance to NVB（χ2=5.209,P=0.022）,GEM（χ2=4.769,P=0.029）,VP-16（χ2=4.596,P=0.032）,and DDP（χ2=6.086,P=0.014）,but not associated with resistance to DOC（χ2=0.430,P=0.512）.Conclusion MTT chemosensitivity assay can effectively predict clinical chemotherapy sensitivity.

关 键 词：基因 多药耐药基因1 非小细胞肺癌 化疗药物 原代培养 药物敏感试验 

分 类 号：R734.2[医药卫生—肿瘤]