Gene expression associated with gemcitabine resistance and its reversal by bexarotene

Resistance of Calu3 NSCLC cells to the cytotoxic nucleoside analog gemcitabine (2',2'-difluorodeoxycytidine) can be prevented as well as reversed by the rexinoid X receptor selective agonist bexarotene. This study was designed to investigate the changes in gene expression associated with gemcitabine resistance and its reversal by bexarotene. In addition to the parental Calu3 cells and the 10 cycles of treatment of the gemcitabine resistant Calu3 cells with vehicle or bexarotene, analogous treatment paradigms with gemcitabine alone as well as the combination of both compounds have been included as controls. (However, it has to be noted that in the combination treatment, cells that were re-sensitized by bexarotene have largely been removed from the culture before harvest due to the cytotoxic activity of gemcitabine.) Keywords: cell type comparison, compound effects From each of the different Calu3 cultures (parental, gemcitabine-resistant treated with vehicle, bexarotene, gemcitabine, or with the gemcitabine/bexarotene combination for 10 cyclesof ten days each) 4 replicate RNA samples were prepared and individually subjected to microarray analysis.