Treatment and survival study in the C57BL/6J-APC(Min)/+(Min) mouse with R-flurbiprofen

Life Sci. 2000 Jan 14;66(8):745-53. doi: 10.1016/s0024-3205(99)00645-1.


Our previous studies with the mouse model of familial adenomatous polyposis (FAP), C57BL/6J-APC(Min)/+ or Min mouse, demonstrated the optimal dose for adenoma reduction with R-flurbiprofen was 10 mg/kg/day as an undivided dose. Divided doses exhibited no increased efficaciousness. This study examines 10 mg/kg R-flurbiprofen daily (qd) on survival as well as a second daily (q.o.d.) schedule and compares it with sulindac sulfone. The q.o.d. schedule at 10 mg/kg was equally efficacious as qd treatment at the same dose. For the q.o.d. group, tumor number decreased similarly (p<0.01); while body weight gain (p<0.01), hematocrit and average tumor area (both, p<0.05) were improved compared with qd treatment. Treatment with R-flurbiprofen (10 mg/kg/day) increased survival significantly (p=0.0004, log-rank) compared to vehicle treated animals. Major biological endpoints (hematocrit, weight gain, tumor number, average and total area [99% reduction]) were significantly improved in treated animals (p<0.01). Sulindac sulfone treatment (50 mg/kg/day) of the Min mouse produced no significant biological benefit. The dose schedule study suggests that for tumor reduction it is necessary to attain a threshold drug-level but not necessarily sustain it over 24 hrs (pharmacodynamic t1/2 >> pharmacokinetic t1/2). During the period of administration R-flurbiprofen dramatically prolongs survival for the mouse model of the human disease, FAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / mortality
  • Adenomatous Polyposis Coli / prevention & control*
  • Alleles
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Colon / pathology
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control
  • Cyclooxygenase Inhibitors / therapeutic use
  • Female
  • Flurbiprofen / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulindac / therapeutic use
  • Survival Analysis
  • Ulcer / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Sulindac
  • Flurbiprofen