背景与目的筛选小细胞肺癌(small cell lung cancer,SCLC)和非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞株中与健择(gemcitabine hydrochloride,GEM)和顺铂(cisplatin,CDDP)药物敏感性相关的基因,有助于进一步阐明抗癌药物作用机制,为克服抗癌药物的耐药性、研制开发新的抗癌药物提供新线索,同时也将为临床的个体化治疗提供理论依据。方法采用MTT比色分析法测定4株SCLC细胞株和6株NSCLC细胞株对CDDP和GEM的药物敏感性,同时应用cDNA macroarray技术检测10株肺癌细胞株中1291个药物敏感性相关基因的表达状态,分析二者之间的相关性。结果与GEM药物敏感性呈明显正相关(r≥0.632,P〈0.05)的基因有6个;与CDDP药物敏感性关联的基因共有45个;与GEM、CDDP敏感性关联(r≥±0.4)的基因有41个;肺癌细胞系中与GEM和CDDP两类药物敏感性呈明显相关的基因是Metallothinein(信号转导分子)、CathepsinB(组织蛋白酶B)和TIMP1(生长因子);肺癌细胞系中与GEM、CDDP药物敏感性相关联的基因主要分布于Metallothinein、Cathepsin B、生长因子TIMP1等类别。结论SCLC和NSCLC细胞株中GEM、CDDP存在药物敏感性相关基因,其中Metallothinein、Cathepsin B和TIMP1基因与GEM药物敏感性呈正相关,与CDDP药物敏感性呈负相关。
Background and objective Screening of small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines with gemcitabine hydrochloride (GEM) and cisplatin (CDDP) related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual. Methods The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized. Results There were 6 genes showing significant positive correlation (r〉0.632, P〈0.0S) with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r≥± 0.4). Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules), Cathepsin B (Organization protease B) and TIMP1 (Growth factor); the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories. Conclusion There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathela- sin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.