Prevention of mouse lung tumors by combinations of chemopreventive agents using concurrent and sequential administration.

BACKGROUND

Concurrent and sequential administration of combinations of budesonide, bexarotene, suberoylanilide hydroxamic acid (SAHA) and atorvastatin were evaluated in A/J mice for prevention of lung tumors initiated by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol, NNK).

MATERIALS AND METHODS

Individual drugs and their combinations were administered for 26 weeks after NNK initiation. For sequential administration, budesonide was given for 21 weeks followed by a second drug.

RESULTS

Alone, budesonide, bexarotene, and SAHA caused a significant decrease in total and large tumors at 21 and 26 weeks. Concurrent treatment with budesonide and bexarotene or SAHA caused a significantly greater decrease in total tumors and large tumors than either drug administered alone. Sequential administration of all combinations (except budesonide/atorvastatin) gave a significant reduction in total and large tumors. Budesonide followed by SAHA and SAHA with atorvastatin yielded a greater reduction in large tumors.

CONCLUSION

Combinations of drugs demonstrated a greater efficacy in preventing mouse lung tumors than did the individual agents.