Al-Wadei Hussein A N, Schuller Hildegard M
Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA; Sana'a University, Sana'a, Yemen.
Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.
Eur J Cancer. 2009 May;45(7):1257-1264. doi: 10.1016/j.ejca.2008.10.035. Epub 2009 Feb 28.
beta-Carotene has shown cancer-preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that beta-carotene stimulates cAMP signalling in vitro. Here, we have tested the hypothesis that beta-carotene promotes the development of pulmonary adenocarcinoma (PAC) in vivo via cAMP signalling.
PAC was induced in hamsters with the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), followed by beta-carotene for 1.5 years. Incidence, multiplicity and size of lung tumours were recorded, and phosphorylated CREB and ERK1/2 in tumour cells were determined by Western blots. Cyclic AMP in blood cells was analysed by immunoassays, retinoids in serum and lungs by HPLC.
beta-Carotene increased lung tumour multiplicity, lung tumour size, blood cell cAMP, serum and lung levels of retinoids and induced p-CREB and p-ERK1/2 in lung tumours.
Our data suggest that beta-carotene promotes the development of PAC via increased cAMP signalling.
β-胡萝卜素在临床前研究中显示出癌症预防作用，但在临床试验中却增加了肺癌死亡率。我们已经表明β-胡萝卜素在体外可刺激环磷酸腺苷（cAMP）信号传导。在此，我们检验了β-胡萝卜素通过cAMP信号传导在体内促进肺腺癌（PAC）发展这一假设。
用致癌物4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）诱导仓鼠发生PAC，随后给予β-胡萝卜素1.5年。记录肺肿瘤的发生率、数量和大小，并通过蛋白质免疫印迹法测定肿瘤细胞中磷酸化的环磷腺苷反应元件结合蛋白（CREB）和细胞外信号调节激酶1/2（ERK1/2）。通过免疫分析测定血细胞中的环磷酸腺苷，通过高效液相色谱法测定血清和肺中的类视黄醇。
β-胡萝卜素增加了肺肿瘤数量、肺肿瘤大小、血细胞环磷酸腺苷、血清和肺中的类视黄醇水平，并诱导肺肿瘤中磷酸化的CREB和磷酸化的ERK1/2。
我们的数据表明，β-胡萝卜素通过增加cAMP信号传导促进PAC的发展。
