目的筛选小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)细胞株中与顺铂(DDP)药物敏感性相关的基因。方法采用二苯基溴化四氮唑蓝(MTT)比色分析法,测定4株SCLC细胞株和6株NSCLC细胞株对DDP的药物敏感性;应用cDNA微阵列技术检测肺癌细胞株中1291个药物敏感性相关基因的表达状态,并分析基因表达与DDP敏感性之间的相关性。结果Metallothionein、CathepsinB、TIMP1、TNF-R1、TGFβ-induced 68000、Cathepsin L、Galectin-1、Annexin 11、PAI-1、IGFBP4、UPAR、Jagged、CDl3、etlA.AR、EphA2(Eck)、APC、RhoC、Fibromodulin、GATA-6、HSC70共20个基因,在SCLC和NSCLC细胞株中均与DDP的药物敏感性呈负相关,只有Procoagula和MDM2与DDP的敏感性呈正相关。VHL、MMP-7、ElonginA、GSK-3B、SLC、Galectin-3、Integrinβ5、Moesin、IKKβ和ETV1等10个基因,只在SCLC细胞株中与DDP的药物敏感性呈负相关,而AT2与DDP敏感性呈正相关。Clusterin、FG FR-2、Thrombospondin 1、HSP 32、Lactate dehydrogenase A、P300、Thymosinβ10、CD81、C/EBPγ和Rak等10个基因,只在NSCLC细胞株中与DDP的药物敏感性呈负相关,而只有CaMKK和TPA与DDP的敏感性呈正相关。结论与DDP药物敏感性相关的基因共有45个,其中共同表达于SCLC和NSCLC细胞株中的基因有22个,在SCLC细胞株中特异表达的基因有11个,在NSCLC细胞株中特异表达的基因有12个。
Objective To search for genes related to cisplatin (DDP) sensitivity in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines. Methods The sensitivity of 4 SCLC lines and 6 NSCLC lines to DDP was evaluated by MTT assay. The expression of 1291 genes related to DDP- sensitivity in the 10 cell lines was measured by cDNA macroarray and the relationship between genes and DDP-sensitivity was analyzed. Results 20 genes were negatively related to DDP-sensitivity in the SCLC and NSCLC cell lines, including Metallothionein, Cathepsin B, TIMP1, TNF-R1, TGFβ-induced 68 000, Cathepsin L, Galectin-1, Annexin 11, PAI-1, IGFBP4, UPAR, Jagged, CD13, α1 A-AR, EphA2 (Eck), APC, RhoC, Fibromodulin, GATA-45 and HSC 70, while only procoagula and MDM2 were positively related to DDP-sensitivity in the SCLC and NSCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the SCLC cell lines, including VHL,MMP-7, Elongin A, GSK-313, SLC, Galectin-3, integrinβ5, moesin, IKKβ, and ETV 1, while only AT2 was positively related to DDP-sensitivity in the SCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the NSCLC cell lines, including Clusterin, FG FR-2, Thrombospondin 1, HSP 32, Lactate dehydrogenase A, P300, Thymosinβ10, CDS1, C/EBPγ, Rak, while only CaMKK and TPA were positively related to DDP-sensitivity in the NSCLC cell lines. Conclusion There were 45 genes related to DDP-sensitivity in 10 lung cancer cell lines. There were 22 co-expressed genes in both SCLC and NSCLC cell lines, and only 11 and 12 genes expressed in the SCLC and NSCLC cell lines, respectively.