贝沙罗汀和布地奈德在小细胞肺癌基因工程小鼠模型中的预防作用。
Preventive effects of bexarotene and budesonide in a genetically engineered mouse model of small cell lung cancer.
机构信息
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.
出版信息
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.
摘要
在本研究中，我们使用 Rb1 和 p53 肺特异性敲除模型，研究了贝沙罗汀（Targretin）和布地奈德在小细胞肺癌化学预防中的作用。贝沙罗汀治疗可显著降低肿瘤发生率、数量和负荷（P<0.05）。布地奈德治疗呈抑制趋势，但无统计学意义（P>0.05）。免疫组化染色表明，贝沙罗汀治疗可减少肿瘤细胞增殖并增加细胞凋亡。Rb1/p53 基因靶向小鼠似乎是人类小细胞肺癌化学预防研究的有价值模型。我们的结果表明，视黄醇 X 受体激动剂贝沙罗汀可能是这种癌症类型的有效化学预防剂。
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本文引用的文献
1
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Clin Cancer Res. 2008 Jul 15;14(14):4556-63. doi: 10.1158/1078-0432.CCR-08-0040.
2
Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells.
Oncogene. 2007 Nov 1;26(50):7111-21. doi: 10.1038/sj.onc.1210524. Epub 2007 May 14.
3
Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes.
J Neuroimmunol. 2007 Feb;183(1-2):50-9. doi: 10.1016/j.jneuroim.2006.11.007. Epub 2006 Dec 18.
4
Effects of glucocorticoids on the growth and chemosensitivity of carcinoma cells are heterogeneous and require high concentration of functional glucocorticoid receptors.
World J Gastroenterol. 2005 Oct 28;11(40):6373-80. doi: 10.3748/wjg.v11.i40.6373.
5
Prevention of mouse lung tumors by targretin.
Int J Cancer. 2006 May 1;118(9):2359-62. doi: 10.1002/ijc.21618.
6
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Oncogene. 2006 Mar 2;25(9):1320-9. doi: 10.1038/sj.onc.1209180.
7
Mouse models for human lung cancer.
Genes Dev. 2005 Mar 15;19(6):643-64. doi: 10.1101/gad.1284505.
8
Nonclassical retinoids and lung carcinogenesis.
Clin Lung Cancer. 2005 Jan;6(4):237-44. doi: 10.3816/CLC.2005.n.003.
9
Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model.
Cancer Cell. 2003 Sep;4(3):181-9. doi: 10.1016/s1535-6108(03)00220-4.
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