Monitoring the expression profiles of doxorubicin-induced and doxorubicin-resistant cancer cells by cDNA microarray

Drug resistance in cancer is a major obstacle to successful chemotherapy, C ancer cells exposed to antitumor drugs may be directly induced to express a subset of genes that could confer resistance, thus allowing some cells to escape killing and form the relapsed resistant tumor, Alternatively, some c ancer cells may be expressing an array of genes that could confer intrinsic resistance, and exposure to cytotoxic drugs select for the survival of the se cells that form the relapsed tumor. We have used cDNA microarray to moni tor the expression profiles of MCF-7 cells that are either transiently trea ted with doxorubicin or selected for resistance to doxorubicin, Our results showed that transient treatment with doxorubicin altered the expression of a diverse group of genes in a time-dependent manner. A subset of the induc ed genes was also found to be constitutively overexpressed in cells selecte d for resistance to doxorubicin, This distinct set of overlapping genes may represent the signature profile of doxorubicin-induced gene expression and resistance in cancer cells. Our studies demonstrate the feasibility of obt aining potential molecular profile or fingerprint of anticancer drugs in ca ncer cells by cDNA microarray, which might yield further insights into the mechanisms of drug resistance and suggest alternative methods of treatment.