title: Preventive effects of bexarotene and budesonide in a genetically engineered mouse model of small cell lung cancer.
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.
authors.affiliation: Department of Surgery and The Alvin J. Siteman Cancer Center and Division of Comparative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Wen
authors.forename: Yijun
authors.initials: Y
authors.lastname: Yi
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Lubet
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D000077610:Bexarotene; D019819:Budesonide / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005818:Genetic Engineering; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019426:Integrases / Q000378:metabolism; D008175:Lung Neoplasms / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D016160:Retinoblastoma Protein / Q000502:physiology; D055752:Small Cell Lung Carcinoma / Q000517:prevention & control*; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D016160:Retinoblastoma Protein; D013764:Tetrahydronaphthalenes; D016159:Tumor Suppressor Protein p53; D019819:Budesonide; D000077610:Bexarotene; C045073:Cre recombinase; D019426:Integrases