Campling B G, Young L C, Baer K A, Lam Y M, Deeley R G, Cole S P, Gerlach J H
Cancer Research Laboratory, Department of Oncology, Queen's University, Kingston, Ontario, K7L 3N6 Canada.
Clin Cancer Res. 1997 Jan;3(1):115-22.
Acquired multidrug resistance is a major obstacle to a cure for small cell lung cancer (SCLC). Overexpression of the MDR1 gene occurs infrequently in multidrug-resistant SCLC cell lines. The multidrug resistance protein (MRP) can confer multidrug resistance, but its role in clinically acquired drug resistance is unknown. The purpose of this study was to measure expression of MRP and MDR1 mRNA in cell lines and clinical samples from SCLC patients and to correlate the results with drug sensitivity profiles. Twenty-three SCLC cell lines and 10 tumor samples from SCLC patients were examined. Samples expressing MRP and MDR1 were identified by reverse transcription-PCR, and levels of MRP mRNA in the cell lines were measured by quantitative reverse transcription-PCR. One of 23 cell lines (4%) expressed MDR1 mRNA, whereas MRP expression was detected in 19 of 23 cell lines (83%). There was a significant correlation between doxorubicin resistance and MRP expression levels (r = 0.422; P = 0.045). Of the 10 clinical samples, 3 expressed only MRP, 2 expressed only MDR1, and 4 expressed both drug resistance genes. In summary, MRP is frequently expressed in clinical samples and cell lines from SCLC patients, and the levels correlate with doxorubicin resistance in unselected SCLC cell lines. Expression of MDR1 can be detected in clinical samples of SCLC but is rarely found in cell lines from drug-resistant patients. These multidrug resistance proteins may contribute to the multifactorial problem of clinically acquired drug resistance in SCLC.
获得性多药耐药是小细胞肺癌（SCLC）治愈的主要障碍。MDR1基因的过表达在多药耐药的SCLC细胞系中很少发生。多药耐药蛋白（MRP）可导致多药耐药，但其在临床获得性耐药中的作用尚不清楚。本研究的目的是检测SCLC患者细胞系和临床样本中MRP和MDR1 mRNA的表达，并将结果与药物敏感性谱相关联。检测了23个SCLC细胞系和10例SCLC患者的肿瘤样本。通过逆转录PCR鉴定表达MRP和MDR1的样本，并通过定量逆转录PCR测量细胞系中MRP mRNA的水平。23个细胞系中有1个（4%）表达MDR1 mRNA，而23个细胞系中有19个（83%）检测到MRP表达。阿霉素耐药与MRP表达水平之间存在显著相关性（r = 0.422；P = 0.045）。在10个临床样本中，3个仅表达MRP，2个仅表达MDR1，4个表达两种耐药基因。总之，MRP在SCLC患者的临床样本和细胞系中频繁表达，其水平与未选择的SCLC细胞系中的阿霉素耐药相关。MDR1的表达可在SCLC临床样本中检测到，但在耐药患者的细胞系中很少发现。这些多药耐药蛋白可能导致SCLC临床获得性耐药这一多因素问题。
