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Preventive effects of bexarotene and budesonide in a genetically engineered mouse model of small cell lung cancer
Yian Wang1, Weidong Wen, Yijun Yi
1Department of Surgery and The Alvin J. Siteman Cancer Center and Division of Comparative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
In the present study, we examined the effect of bexarotene (Targretin) and budesonide in the chemoprevention of small cell lung carcinoma using a lung-specific knockout model of Rb1 and p53. Upon treatment with bexarotene, tumor incidence, number, and load were significantly reduced (P < 0.05). Budesonide treatment trended to inhibition, but the effect was not statistically significant (P > 0.05). Immunohistochemical staining indicated that bexarotene treatment decreased cell proliferation and increased apoptosis in tumors. The Rb1/p53 gene-targeted mouse seems to be a valuable model for chemopreventive studies on human small cell lung cancer. Our results indicate that the retinoid X receptor agonist bexarotene may be a potent chemopreventive agent in this cancer type.
Insights
Bexarotene significantly reduced tumor development in a mouse model of small cell lung cancer (SCLC). This retinoid X receptor agonist shows potential as a chemopreventive agent for SCLC.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Small cell lung cancer (SCLC) presents a significant therapeutic challenge.
- Identifying effective chemopreventive strategies is crucial for reducing SCLC incidence and progression.
Purpose of the Study:
- To evaluate the chemopreventive efficacy of bexarotene and budesonide in a genetically engineered mouse model of SCLC.
- To investigate the impact of these agents on tumor development, proliferation, and apoptosis.
Main Methods:
- Utilized a lung-specific knockout mouse model targeting Rb1 and p53 genes to mimic SCLC.
- Administered bexarotene and budesonide to assess their effects on tumor incidence, number, and load.
- Performed immunohistochemical staining to analyze cell proliferation and apoptosis markers.
Main Results:
- Bexarotene treatment led to a statistically significant reduction in SCLC tumor incidence, number, and load (P < 0.05).
- Budesonide showed a trend towards tumor inhibition, but the results were not statistically significant (P > 0.05).
- Immunohistochemistry confirmed that bexarotene decreased tumor cell proliferation and increased apoptosis.
Conclusions:
- The Rb1/p53 gene-targeted mouse model is a valuable tool for SCLC chemoprevention research.
- Bexarotene demonstrates potent chemopreventive activity against SCLC in this preclinical model.
- Further investigation into bexarotene as a chemopreventive agent for SCLC is warranted.
