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 containing medium for several months and the expression of the MDR phenotype was followed through the analysis of the expression and functionality of the P-glycoprotein (Pgp), the chemosensitivity to daunorubicin (DNR), and the mRNA expression of mdr-1, multidrug resistance-associated protein (MRP), and topoisomerase IIalpha and IIbeta genes. Replacement of OF by penicillin streptomycin (PS) resulted in a significant decrease in mdr-1 mRNA expression, which was found to correlate with a decrease in the expression and functionality of the Pgp. After antibiotic starvation for 4 weeks, cells grown in antibiotic-free medium were then exposed to PS or OF; these cells showed an increase in mdr-1 mRNA/Pgp and MRP mRNA expression without a decrease in DNR cytotoxicity. OF cultured cells exhibited a significant increase in Pgp expression without evidence of the functionality of the Pgp. An increase in topoisomerase IIalpha mRNA expression was observed with time and with the number of passages of the cell line without any relationship to the presence 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.
Marchal
S
S
Centre Alexis Vautrin, Laboratoire de Recherche en Oncologie, Vandoeuvre les Nancy, France. s.marchal@nancy.fnclcc.fr
Merlin
J L
JL
Colosetti
P
P
Finance
C
C
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000235:genetics; D003630:Daunorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015242:Ofloxacin / Q000494:pharmacology*; D010406:Penicillins / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004264:DNA Topoisomerases, Type I; D003630:Daunorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015242:Ofloxacin; D010406:Penicillins; D013307:Streptomycin