Related Experiment Video
Updated: Aug 22, 2026
Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment
Published on: June 28, 2018
Budesonide exerts its chemopreventive efficacy during mouse lung tumorigenesis by modulating gene expressions
Ruisheng Yao1, Yian Wang, William J Lemon
1Department of Surgery and The Alvin J Siteman Cancer Center, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA.
Abstract:
Budesonide, a glucocorticoid, was proven to be a highly effective agent in preventing the development of lung tumors in A/J mice. In a lung tumor bioassay, budesonide produced 70% inhibition of tumor multiplicity and 94% reduction of total tumor load compared to benzopyrene (B[a]P) treated mice. Gene expression array analysis was performed on mouse lung tumors from this bioassay using Affymetrix U74Av2 GeneChips to determine gene expression changes associated with budesonide treatment. We found 363 genes that were changed between lung tumors induced by treatment with B[a]P and similar tumors treated with budesonide. Among them, 243 genes were overexpressed and 120 genes were underexpressed after budesonide treatment. In addition, 108 genes differentially expressed during mouse lung tumorigenesis (50 genes overexpressed and 58 genes underexpressed) were modulated back to normal levels after budesonide treatment when compared with the controls group. These genes are involved in a broad range of different pathways including control of cell cycle, signal transduction, and apoptosis and may play a role in the observed preventive effect. Our results suggest that budesonide exerts its effects of chemoprevention through growth arrest via Mad2/3 and through apoptosis via Bim/Blk and, by inference, caspase-8/9. Using the pathway visualization tool GenMapp, G protein pathway and MAPK cascade were also regulated by budesonide. Thus, we have determined, for the first time, the expression profiles of genes modulated by budesonide during murine lung tumorigenesis. Our results indicate that the chemopreventive effects of budesonide in the mouse lung tumorigenesis assay involved increase and decrease expression of a wide variety of genes in multiple signaling pathways.
Insights
Budesonide effectively prevents lung tumors in mice by altering gene expression. This glucocorticoid inhibits tumor growth and load, offering new insights into chemoprevention strategies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Lung cancer remains a significant global health challenge.
- Glucocorticoids, like budesonide, are explored for potential chemopreventive properties.
- Understanding molecular mechanisms of chemoprevention is crucial for developing new therapies.
Purpose of the Study:
- To investigate the gene expression changes induced by budesonide treatment in a mouse lung tumor model.
- To elucidate the molecular pathways targeted by budesonide for its chemopreventive effects.
Main Methods:
- A/J mice were used in a lung tumor bioassay with budesonide and benzo[a]pyrene (B[a]P).
- Gene expression profiling was performed on lung tumors using Affymetrix U74Av2 GeneChips.
- Bioinformatic tools, including GenMapp, were utilized for pathway analysis.
Main Results:
- Budesonide significantly inhibited tumor multiplicity (70%) and total tumor load (94%) compared to B[a]P.
- Gene expression analysis revealed 363 differentially expressed genes in budesonide-treated tumors.
- Budesonide modulated genes involved in cell cycle control, apoptosis, G protein signaling, and MAPK cascade.
Conclusions:
- Budesonide demonstrates potent chemopreventive effects against lung tumorigenesis in mice.
- The mechanism involves growth arrest (Mad2/3) and induction of apoptosis (Bim/Blk, caspase-8/9).
- Budesonide regulates multiple signaling pathways, providing a comprehensive understanding of its anti-cancer activity.
