背景化疗是胰腺的 ductal 腺癌(PDAC ) 的最经常采用的辅助治疗,但是药抵抗的发展减少它的有效性。multidrug 抵抗(MDR ) 的机制的澄清在 PDAC 的开发被需要改进化疗的治疗学的效果。这研究被瞄准调查 PDAC 的 MDR 的分子的机制并且识别与基因表示房间线 SW1990 和三选择药的胰腺的 chemoresistant 介绍的 MDR development.Methods 联系的基因亚线, SW1990/5-Fu , SW1990/ADM 和 SW1990/GEM ,用 oligonucleotide microarray 被获得( Affymetrix HG U133 2.0 加)那包含了约 38 000 人的基因。 microarray 结果被即时量的聚合酶链反应验证,在那里的西方的污点 analysis.Results 是 165 基因并且表示了顺序标签,其中一些从来没被连接过到药抵抗,那是在所有抵抗亚线的起来调整或下面调整的至少2褶层什么时候与到基因本体论注解的 SW1990.According 相比,差别在胰腺的癌症表示了与 MDR 有关的基因属于许多功能的家庭并且与多样的生物过程与抗氧化剂活动, apoptosis,房间周期,信号 transduction 和细胞内部的粘附有关的基因可以经历先于 MDR 开发的 epigenetic 变化。一个层次聚类被进行,几有趣的簇被发现那可能主要与房间周期和发展规定有关。在支持向量机器(SVM ) 分析,和预言结果被细胞毒素的测试检验以后,一条预言规则从 117 基因的表示侧面被造。作为结果,一个微分基因表示模式在 multidrug 被构造抵抗胰腺的癌症 cells.Conclusions 这研究的调查结果证明基于基因表示模式,一条 chemoresistance 预言规则的建设是实际的。这些数据提供新卓见进胰腺的癌症 MDR 开发的分子的机制并且可能为在胰腺的癌症病人的 MDR 的察觉和治疗有用。
Background Chemotherapy is the most frequently adopted adjuvant therapy of pancreatic ductal adenocarcinoma (PDAC), but the development of drug resistance reduces its effectiveness. Clarification of the mechanism of multidrug resistance (MDR) development in PDAC is needed to improve the therapeutic effect of chemotherapy. This study was aimed to investigate the molecular mechanism of MDR of PDAC and to identify genes associated with MDR development. Methods The gene expression profiles of cell line SW1990 and three drug-selected pancreatic chemoresistant sub-lines, SW1990/5-Fu, SW1990/ADM and SW1990/GEM, were obtained using an oligonucleotide microarray (Affymetrix HG U133 2.0 plus) that contained approximately 38 000 human genes. The microarray results were validated by real-time quantitative polymerase chain reaction and Western blot analysis. Results There were 165 genes and expressed sequence tags, some of which have never been linked to drug resistance, that were up- or down-regulated at least 2-fold in all resistant sub-lines when compared with SW1990. According to Gene Ontology annotation, differentially expressed genes related to MDR in pancreatic cancer belong to many functional families and with diverse biological processes. Genes related to antioxidant activity, apoptosis, the cell cycle, signal transduction and intracellular adhesion may undergo epigenetic changes preceding MDR development. A hierarchical clustering was conducted and several interesting clusters were discovered that may be primarily related to cell cycle and developmental regulation. A prediction rule was built from the expression profiles of 117 genes after support vector machine (SVM) analysis, and the prediction result was examined by cytotoxic testing. As a result, a differential gene expression pattern was constructed in multidrug resistant pancreatic cancer cells. Conclusions The findings of this study prove that construction of a chemoresistance prediction rule, based on gene expression patterns, is practica