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目的筛选人肺癌细胞株中与去甲长春新碱(NVB)、泰索帝(Doc)药物敏感性相关的基因。方法采用MTT比色分析法,测定4株小细胞肺癌(SCLC)细胞株和6株非小细胞肺癌(NSCLC)细胞株对NVB、Doc的药物敏感性;应用cDNA macroarray技术检测10株肺癌细胞株中1291个药物敏感性关联基因的表达状态,聚类分析二者间的相关性。结果(1)NVB对10株肺癌细胞株的作用效果明显优于Doc。(2)10株肺癌细胞株中,与Doc呈正相关的药物敏感性关联基因多于NVB,而与NVB呈负相关的多于Doc;而在6株NSCLC中,与Doc和NVB呈正相关、负相关一致的基因较多。(3)10株肺癌细胞株中,有51个基因与Doc、NVB药物敏感性相关联,占全部候选基因的3.95%(51/1291)。与NVB药物敏感性呈显著相关的基因27个,其中负相关24个,正相关3个;与Doc药物敏感性关联的基因24个,其中负相关13个,正相关11个。6株NSCLC株中,有67个基因与药物敏感性相关,占全部实验基因的5.19%(67/1291)。与NVB药物敏感性呈显著相关的基因29个,其中负相关25个,正相关4个;与Doc药物敏感性关联的基因38个,其中负相关34个,正相关4个。(4)Rab1、Rab3、Rho B、Rho C、Rac1、Rac2、Gho GDIβ、CD44、Integrinα5、Integrinα6、Integrinβ5、Vinculin等细胞骨架关联基因在SCLC、NSCLC中的表达存在差异。结论SCLC和NSCLC细胞株中,NVB、Doc药物敏感性相关联基因表达存在明显差异。
Objective To screen the genes related to the drug susceptibility of vinorelbine (NVB) and Docetaxel (Doc) in human lung cancer cell lines. Methods MTT colorimetric assay was used to determine the drug sensitivity of 4 small cell lung cancer (SCLC) cell lines and 6 non-small cell lung cancer (NSCLC) cell lines to NVB and Doc. The cDNA microarrays were used to detect the expression of 10 lung cancer cell lines In 1291 drug sensitivity related gene expression status, cluster analysis of the correlation between the two. Results (1) The effect of NVB on 10 lung cancer cell lines was significantly better than that of Doc. (2) Of the 10 lung cancer cell lines, positive drug-related genes were more than NVB, negatively correlated with NVB, and positive with Doc and NVB in 6 NSCLC samples, negative Relevant genes more. (3) Of the 10 lung cancer cell lines, 51 genes were associated with the drug sensitivity of Doc and NVB, accounting for 3.95% (51/1291) of all the candidate genes. There were 27 genes that were significantly correlated with drug sensitivity of NVB, of which 24 were negative and 3 were positive. 24 genes were associated with drug susceptibility to Doc, of which 13 were negative and 11 were positive. Of the six NSCLC strains, 67 genes were associated with drug sensitivity, accounting for 5.19% (67/1291) of all experimental genes. There were 29 genes that were significantly correlated with the drug sensitivity of NVB, of which 25 were negative and 4 were positive. 38 genes were associated with Doc drug sensitivity, of which 34 were negative and 4 were positive. (4) The expression of Rab1, Rab3, Rho B, Rho C, Rac1, Rac2, Gho GDIβ, CD44, Integrinα5, Integrinα6, Integrinβ5, Vinculin and other cytoskeleton related genes in SCLC and NSCLC were different. Conclusion There is a significant difference in the gene expression of NVB and Doc in SCLC and NSCLC cell lines.