Investigating the Effects of DNA Demethylation in Chemotherapy Resistance by ChIP-on-Chip Method

Abstract

OBJECTIVEThis study aimed to determine the epigenetic basis of drug resistance mechanisms developed in MCF-7breast cancer cell line that is resistant to an anticancer agent paclitaxel. Thus, we investigated the effectsof the changes in DNA level on gene expression profile and proposed methods of inhibiting resistanceby DNA modifications.METHODSWe investigated the epigenetic basis of acquired drug resistance in whole genome by comparing chromosome immunoprecipitation in paclitaxel-resistant MCF-7 (MCF-7/Pac) cells and in drug-sensitive(MCF-7/S) cells. For this analysis, DNA samples from both cell lines were immunoprecipitated andlabeled with Cy3 and Cy5 fluorescent dyes. Hybridization and array scanning was performed with Agilent all-Genome Microarray platform that was designed to detect DNA methylation. The obtained highthroughput information was analyzed with a bioinformatics analysis program.RESULTSThe results showed that demethylation and epigenetic modulation of the DNA regions encoding 90genes are significant in the development of multiple drug resistance (MDR) in breast cancer. Some ofthese genes, ICAM4, COX6B2, ITGB8, SLC39A4, TUBB2C, COL6A1, DAPK1, RUNX3, SLC35F3, andMAP6, are important players in the development of drug resistance and cancer stem cells.CONCLUSIONStudies on reversing multidrug resistance can be carried out by DNA modification or methylation oftarget genes regions on DNA. The results presented in this study may shed light on drug developmentstudies to make DNA modifications.