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

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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.