Screening and validation of target molecules involved in mechanism of multi-modality therapy

背景资料：大量证据表明，一些细胞毒性药物在影响细胞信号转导途径方面具有复杂的活性。材料与方法：将人鳞状细胞癌细胞系RERF-LC-AI暴露于低剂量顺铂5天后进行cDNA微阵列分析。通过小干扰RNA抑制上调的基因表达以研究细胞的表型改变。结果：在筛选的30，000个基因中，42个基因在顺铂治疗中表达增加或减少超过2倍。它们包括与细胞凋亡、细胞周期调控和DNA代谢/修复相关的基因。抑制最显着改变的5个基因的小干扰RNA导致部分减少细胞凋亡，而不改变顺铂的细胞毒性。结论：除了对细胞的直接细胞毒性作用外，顺铂可能具有涉及耐药性的间接作用，以及与其他药物的协同作用。

Background: Substantial evidence has disclosed that some cytotoxic agents have complex activities in influencing signal transduction pathways in cells. Materials and Methods: cDNA microarray analysis was performed after exposing a human squamous cell carcinoma cell line, RERF-LC-AI, to low-dose cisplatin for 5 days. Up-regulated gene expressions were suppressed by small interfering RNA to investigate phenotypic alteration of the cells. Results: Among 30,000 genes screened, 42 genes showed increases or decreases in expression of more than 2-fold in cisplatin treatment. They included genes with functions involved in apoptosis, cell cycle regulation and DNA metabolism/repair. Suppression of the most significantly altered 5 genes by small interfering RNA resulted in partly reduced apoptosis without altering cytotoxicity of cisplatin. Conclusion: Besides direct cytotoxic effects on cells, cisplatin may have indirect effects involving drug resistance, and synergistic effects with other agents.