Gene expression profile related to oxaliplatin resistance in a panel of sensitive human colorectal cancer cell lines with acquired resistance to the drug

Abstract

13143 Background: Platinum drugs resistance acquisition is a complex process based in the alteration of genes that belong to several pathways related to drug metabolism. To clarify the multifactoriality of these mechanisms, we analyzed gene expression profile in the four CCR cell lines HT29, LoVo, DLD1 and LS513, and their sublines HTOXAR, LOVOXAR, DLDOXAR y LSOXAR that we induced oxaliplatin resistance in our laboratory. The aim of this work consisted on comparing gene expression profile between resistant cells group (cluster R) and sensitive cells group (cluster S) to determine genes and pathways that could play a role in oxaliplatin resistance acquisition process. Methods: Resistance level determination by MTT assay. Gene expression profile analysis through microarray technology (Human 19K oligo): labeled with Genisphere 3DNA Array350 (Dye Swap), and data analysis using Imagene 4.1, ArrayNorm1.7.2 y Genesis 1.5.0 (ANOVA). Results: According to ANOVA analysis of cluster R versus cluster S, we obtained 32 genes that showed significant changes in expression. 15 of these genes were up regulated and 17 were down regulated. We emphasize genes that belong to pathways previously related to oxaliplatin metabolism (AKT1, TRIP and NLK), family of genes that does not expressed in the same chromosome (KIAA0232 and KIAA0256, SLC39A9 and SLC30A9), and family of genes that had previously related to carcinogenesis processes (KRT19, KRT18 and KRT8). Conclusions: It is possible to develop oxaliplatin resistant CCR cell lines. In our oxaliplatin acquired resistance model, 32 genes showed gene expression changes between groups. These genes belong to signal transduction pathways and cellular integrity mechanisms and they could be a future oxaliplatin resistance prediction profile in colorectal cancer patients. No significant financial relationships to disclose.