Preventive effects of bexarotene and budesonide in a genetically engineered mouse model of small cell lung cancer.
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.
Wang
Yian
Y
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.
Wen
Weidong
W
Yi
Yijun
Y
Zhang
Zhongqiu
Z
Lubet
Ronald A
RA
You
Ming
M
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
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