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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 & AIM: To screen gemcitabine hydrochloride (GEM) and cisplatin (CDDP) in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) Drug sensitivity related genes help to further clarify the mechanism of anti-cancer drugs, to overcome the resistance of anti-cancer drugs, research and development of new anti-cancer drugs provide new clues, but also for clinical individualized treatment theory in accordance with. Methods MTT colorimetric assay was used to determine the drug sensitivity of 4 SCLC cell lines and 6 NSCLC cell lines to CDDP and GEM. CDNA macroarray was used to detect the expression of 1291 drug sensitivity-related genes in 10 lung cancer cell lines , Analyze the correlation between the two. Results There were 6 genes positively correlated with GEM sensitivity (r≥0.632, P <0.05), 45 genes associated with CDDP drug sensitivity, and associated with GEM and CDDP sensitivities (r ≥ ± 0.4) 41 genes were found in lung cancer cell lines; Metallothinein (signal transduction molecule), CathepsinB (cathepsin B) and TIMP1 (growth factor) were significantly correlated with sensitivity of GEM and CDDP in lung cancer cell lines; Genes associated with GEM and CDDP drug sensitivity are mainly found in Metallothinein, Cathepsin B, growth factor TIMP1 and other categories. Conclusion There are drug-sensitive genes related to GEM and CDDP in SCLC and NSCLC cell lines. Metallothinein, Cathepsin B and TIMP1 gene are positively correlated with GEM drug sensitivity and negatively correlated with CDDP drug sensitivity.