Al-Wadei Hussein A N, Schuller Hildegard M
Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Int J Oncol. 2009 Apr;34(4):1093-8. doi: 10.3892/ijo_00000236.
Studies have suggested that retinoids prevent lung cancer by interacting with nuclear retinoid receptors. However, clinical trials with beta-carotene increased lung cancer mortality. We recently showed that beta-carotene stimulates the proliferation of small airway-derived adenocarcinoma by increasing cAMP signaling. Here, we have tested the hypothesis that beta-carotene may stimulate squamous cell carcinoma cells via similar mechanisms. We determined the effects of beta-carotene in cell lines from squamous cell carcinomas and large airway epithelia on proliferation by MTT assays in the presence and absence of inhibitors. Signaling via cAMP/PKA was measured by immunoassays and PKA activation assay. Phosphorylated ERK1/2 was determined by Western blotting. beta-carotene significantly inhibited proliferation and phosphorylation of ERK1/2 by Galphas-mediated signaling involving adenylyl cyclase, cAMP, PKA and ERK1/2. These findings introduce a non-genomic inhibitory mechanism of beta-carotene and emphasize the need for the development of marker-guided lung cancer prevention.
研究表明，类视黄醇通过与核类视黄醇受体相互作用来预防肺癌。然而，β-胡萝卜素的临床试验却增加了肺癌死亡率。我们最近发现，β-胡萝卜素通过增加环磷酸腺苷（cAMP）信号传导来刺激小气道来源的腺癌增殖。在此，我们检验了β-胡萝卜素可能通过类似机制刺激鳞状细胞癌细胞的假说。我们通过MTT法，在有或没有抑制剂的情况下，测定了β-胡萝卜素对鳞状细胞癌和大气道上皮细胞系增殖的影响。通过免疫测定和蛋白激酶A（PKA）激活试验来检测cAMP/PKA信号传导。通过蛋白质印迹法测定磷酸化的细胞外信号调节激酶1/2（ERK1/2）。β-胡萝卜素通过涉及腺苷酸环化酶、cAMP、PKA和ERK1/2的Gαs介导的信号传导，显著抑制ERK1/2的增殖和磷酸化。这些发现引入了β-胡萝卜素的一种非基因组抑制机制，并强调了开发标志物引导的肺癌预防方法的必要性。
