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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 evaluate the chemosensitivity of MTT drug sensitivity test combined with multidrug resistance gene 1 (MDR1) in the diagnosis of primary non-small cell lung cancer (NSCLC) and provide the basis for clinical individualized treatment. Methods Eighty patients with NSCLC (46 males and 34 females; median age 54 (29-81) years) surgically resected in Central Hospital of Zibo from 2009 to 2011 were enrolled in this study. MTT drug sensitivity test was used to detect patients’ (DDP), gemcitabine (GEM), docetaxel (DOC), etoposide (VP-16) and vinorelbine (NVB) in vitro drug sensitivity, using real-time fluorescence quantitative reverse transcription polymerase chain reaction RT-PCR) technique was used to detect the expression of MDR1 in tumor tissues. Results After chemotherapy drugs, NSCLC cells cultured in vitro showed morphological changes, decreased metabolic activity and apoptosis. The sensitivity of different NSCLC cells to different chemotherapeutic drugs was different with NSCLC cells assayed by MTT assay. The sensitivity of NSCLC cells to different chemotherapeutic drugs was also different: the sensitivity to DOC, GEM and VP-16 was higher than that of DDP and 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). The positive expression rate of MDR1 in tumor tissues was 40.0% (32/80). The positive expression of MDR1 had no correlation with tumor histological type, differentiation degree, lymph node metastasis and TNM stage (P> 0.05). The positive expression of MDR1 was positively correlated with the ratio of NVB (χ2 = 5.209, P = 0.022), GEM (χ2 = 4.769, P = 0.029), VP- 16 (χ2 = 4.596, P = 0.032) and DDP In vitro drug resistance was correlated with DOC resistance (χ2 = 0.430, P = 0.512). Conclusion MTT drug sensitivity test can effectively predict the sensitivity of clinical chemotherapeutic drugs. MTT drug sensitivity test combined with MDR1 test can improve the sensitivity of NSCLC chemotherapy and guide its individualized treatment.