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Prevention of mouse lung tumors by combinations of chemopreventive agents using concurrent and sequential
Bruce C Casto1, Michael A Pereira
1College of Public Health, The Ohio State University, Columbus, OH 43210, U.S.A. casto.44@osu.edu
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.
Insights
Combining budesonide, bexarotene, and suberoylanilide hydroxamic acid (SAHA) effectively prevents lung tumors in mice. Drug combinations showed greater efficacy than individual agents in this chemoprevention study.
Area of Science:
- Oncology
- Pharmacology
- Preclinical Research
Background:
- Lung cancer chemoprevention strategies are crucial for reducing cancer incidence.
- Investigating drug combinations for enhanced efficacy in cancer prevention.
Purpose of the Study:
- To evaluate the efficacy of concurrent and sequential administration of budesonide, bexarotene, SAHA, and atorvastatin in preventing NNK-initiated lung tumors in A/J mice.
Main Methods:
- A/J mice were initiated with NNK and subsequently treated with individual drugs or combinations for 26 weeks.
- Sequential administration involved budesonide followed by a second drug for 21 weeks.
Main Results:
- Budesonide, bexarotene, and SAHA alone significantly reduced total and large lung tumors.
- Concurrent and sequential drug combinations demonstrated superior tumor reduction compared to monotherapy.
- Specific combinations like budesonide/SAHA and SAHA/atorvastatin showed enhanced reduction in large tumors.
Conclusions:
- Drug combinations are more effective than individual agents for lung tumor chemoprevention in this mouse model.
- Sequential administration of certain drug combinations offers significant lung tumor reduction.
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