Synergistic antitumor effects of fleroxacin with 5-fluorouracil in vitro and in vivo for bladder cancer cell lines.

Abstract

OBJECTIVES:

To study the antitumor effects of fleroxacin against bladder tumor cell lines and the synergistic effect with 5-fluorouracil (5-FU) both in vitro and in vivo.

METHODS:

In vitro, the MBT-2 and T-24 urothelial carcinoma cell lines were exposed to fleroxacin in concentrations of 0-800 microg/mL for 12, 24, and 48 hours. Cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Synergism of fleroxacin with 5-FU was evaluated using the normalized isobologram and combination index by CalcuSyn for Windows computer program. In vivo, 4-week-old female C57BL/6 mice were orally administered fleroxacin and/or 5-FU 1 week before starting administration of a carcinogenic agent (0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine) for 12 weeks. The mice were killed 8 weeks after the end of administration for histologic evaluation of the urinary bladder.

RESULTS:

Fleroxacin significantly inhibited cell proliferation in a dose- and time-dependent manner at concentrations of 50-800 microg/mL for 12, 24, and 48 hours. The inhibitory effects of fleroxacin combined with 5-FU appeared synergistic using normalized isobologram and combination index analysis. In vivo, no significant changes in bladder tumor frequency were noted between the control and fleroxacin and 5-FU groups. Significant inhibition of tumor frequency was observed only when fleroxacin was administered with 5-FU.

CONCLUSIONS:

Fleroxacin combined with 5-FU inhibited the proliferation of bladder tumor cell lines both in vitro and in vivo. This combination therapy might be applicable in clinical settings.

• Authors: Toru Nishikawa, Yasuo Kohjimoto, Masaya Nishihata, Shoichi Ebisuno, Isao Hara
• Journal: Urology (Urology) Vol. 74 Issue 6 Pg. 1370-6 (Dec 2009) ISSN: 1527-9995 [Electronic] United States
• PMID: 19428092 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Nucleic Acid Synthesis Inhibitors
• Fleroxacin
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (therapeutic use)
• Carcinoma, Transitional Cell (drug therapy)
• Cell Line, Tumor
• Cells, Cultured
• Drug Screening Assays, Antitumor
• Drug Synergism
• Drug Therapy, Combination
• Female
• Fleroxacin (therapeutic use)
• Fluorouracil (therapeutic use)
• Humans
• Mice
• Mice, Inbred C57BL
• Nucleic Acid Synthesis Inhibitors (therapeutic use)
• Urinary Bladder Neoplasms (drug therapy)