化疗前后乳腺癌细胞基因表达谱的变化

Change of gene expression profiles in breast cancer cell lines before and after chemotherapy

目的探讨乳腺癌细胞经化疗药物处理前后分子水平变化特征。方法应用含14000个基因的人cDNA芯片检测经阿霉素(ADM)、5-氟尿嘧啶(5-Fu)、甲氨喋呤MTX)及AF (ADM+5-Fu)和MF(MTX+5-Fu)处理前后MCF-7和MDA-MB-231细胞基因表达谱的变化。结果两种细胞经不同药物处理后基因表达的变化有差异,通过cDNA芯片检测,得到了每种细胞经不同药物处理后差异表达的基因,并初步筛选出经ADM处理后在两个细胞株中均差异表达且表达趋势相同的基因10个,5-Fu处理组49个,MTX处理组8个,AF处理组10个以及MF处理组58个,这些基因涉及细胞骨架、细胞增殖、分化及周期调控、基因转录和翻译以及细胞物质与能量代谢等多方面。结论药物作用所致细胞分子水平的变化复杂,涉及多种途径、多个基因,芯片技术可为筛选化疗敏感基因提供全面、可靠的技术支持。

Objective To investigate the change of gene expression profiles in breast cancer cell lines treated by anticancer drugs. Methods Human cDNA microarray containing 14000 genes was used to analyze the expression profiles of MCF-7 and MDA-MB-231 breast cancer cell lines before and after drug treatment including adriamycin （ADM）, 5-fluorouracil （5-Fu）, methotrexate （MTT） and drug combination of AF （ADM ＋ 5-Fu） and MF （MTX ＋ 5-Fu）. Results There were some differences in gene expression changes between MCF-7 and MDA-MB-231 after drug treatment. A series of genes were selected for each drug treatment. They showed up- or down-expression with significant difference coincidentally in both cell lines. They played important role in multiple process including cytoskeleton, cell proliferation/differentiation, regulation of cell cycle, transcription and translation of gene and metabolism of cells. Conelusion The process of a antieaneer drug killing tumor cells is very complicated involving many gene unregulated or down regulated expression. As a new approach, cDNA mieroarray is feasible to genome wide exploration of gene expression patterns correlated to chemosensitivity.