beta-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma.

beta-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma.
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DOI:
10.1016/j.ejca.2008.10.035
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发表时间:
2009-05
影响因子:
8.4
通讯作者:
Schuller, Hildegard M.
Schuller, Hildegard M.
中科院分区:
医学1区
文献类型:
--
作者:
Al-Wadei, Hussein A. N.;Schuller, Hildegard M.

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β -胡萝卜素在临床前研究中显示出癌症预防作用,而在临床试验中却增加了肺癌死亡率。我们已经证明β-胡萝卜素在体外刺激cAMP信号。在这里,我们验证了β -胡萝卜素通过cAMP信号传导促进体内肺腺癌(PAC)发展的假设。方法:用致癌物4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁酮(NNK)和β-胡萝卜素对仓鼠进行PAC诱导,持续1.5年。记录肺肿瘤的发生率、多样性和大小,Western blots检测肿瘤细胞中CREB和ERK1/2的磷酸化水平。免疫分析法分析血细胞中的环AMP,高效液相色谱法分析血清和肺中的类维生素a。结果:β -胡萝卜素增加了肺肿瘤的多样性、肺肿瘤的大小、血细胞cAMP、血清和肺中类维生素a的水平,并诱导了肺肿瘤的p-CREB和p-ERK1/2。结论:我们的数据表明β -胡萝卜素通过增加cAMP信号通路促进PAC的发展。
Beta-carotene has shown cancer preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that β-carotene stimulates cAMP signaling in vitro. Here, we have tested the hypothesis that beta-carotene promotes the development of pulmonary adenocarcinoma (PAC) in vivo via cAMP signaling. Methods: PAC was induced in hamsters with the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) followed by β-carotene for 1.5 years. Incidence, multiplicity and size of lung tumors were recorded and phosphorylated CREB and ERK1/2 in tumour cells determined by Western blots. Cyclic AMP in blood cells was analysed by immunoassays, retinoids in serum and lungs by HPLC. Results: beta-carotene increased lung tumor multiplicity, lung tumour size, blood cell cAMP, serum and lung levels of retinoids and induced p-CREB and p-ERK1/2 in lung tumours. Conclusions:Our data suggest that beta-carotene promotes the development of PAC via increased cAMP signaling.
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