Preventive effects of bexarotene and budesonide in a genetically engineered mouse model of small cell lung cancer

Cancer Prev Res (Phila). 2009 Dec;2(12):1059-64. doi: 10.1158/1940-6207.CAPR-09-0221. Epub 2009 Nov 24.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Anticarcinogenic Agents / therapeutic use
  • Apoptosis / drug effects
  • Bexarotene
  • Budesonide / therapeutic use*
  • Cell Proliferation / drug effects
  • Disease Models, Animal*
  • Female
  • Genetic Engineering*
  • Immunoenzyme Techniques
  • In Situ Nick-End Labeling
  • Integrases / metabolism
  • Lung Neoplasms / prevention & control*
  • Male
  • Mice
  • Mice, Inbred A
  • Retinoblastoma Protein / physiology
  • Small Cell Lung Carcinoma / prevention & control*
  • Tetrahydronaphthalenes / therapeutic use*
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Retinoblastoma Protein
  • Tetrahydronaphthalenes
  • Tumor Suppressor Protein p53
  • Budesonide
  • Bexarotene
  • Cre recombinase
  • Integrases