Influence of the fluoroquinolone ofloxacin on the intrinsic expression of multidrug resistance phenotype in HCT-8 human colon carcinoma cells

The influence of antibiotics. particularly ofloxacin (OF), a commonly used antimicrobial fluoroquinolone, on the multidrug resistance (MDR) phenotype of the HCT-8 cell line was studied. This cell line was grown in OF containi ng medium for several months and the expression of the MDR phenotype wax fo llowed through the analysis of the expression and functionality of the P-gl ycoprotein (Pgp), the chemosensitivity to daunorubicin (DNR), and the mRNA expression of mdr-l, multidrug resistance-associated protein (MRP), and top oisomerase II alpha and II beta genes. Replacement of OF by penicillin stre ptomycin (PS) reulted in a significant decrease in mdr-l mRNA expression, w hich was found to correlate with a decrease in the expression and functiona lity of the Pgp. After antibiotic starvation For 4 creeks, cells grown in a ntibiotic-free medium were then exposed to PS or OF: these cells showed an increase in mdr-l mRNA/Pgp and MRP mRNA expression without a decrease in DN R cytotoxicity. OF cultured cells exhibited a significant increase in Pgp e xpression without evidence of the functionality of the Pgp. An increase in tapoisomerase II alpha mRNA expression was observed with time and with the number of passages of the cell line without any relationship to the presenc e of antibiotics in the culture medium. These results showed that extensive use of antibiotics. particularly the quinolones, can modify the phenotype of the HCT-8 colon adenocarcinoma cell line.