Kou Yu, Li Lei, Li Hong, Tan Yuhui, Li Bin, Wang Kun, Du Biaoyan
Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
Henan Institute of Orthopedic and Traumatology, Henan Luoyang Orthopedic-Traumatological Hospital, Henan, China.
Biochem Biophys Res Commun. 2016 Oct 14;479(2):290-296. doi: 10.1016/j.bbrc.2016.09.061. Epub 2016 Sep 14.
Berberine is a natural compound extracted from Coptidis rhizoma, and accumulating proof has shown its potent anti-tumor properties with diverse action on melanoma cells, including inhibiting cancer viability, blocking cell cycle and migration. However, the mechanisms of berberine have not been fully clarified. In this study, we identified that berberine reduced the migration and invasion capacities of B16 cells, and notably altered pluripotency of epithelial to mesenchymal transition associated factors. We found that berberine also downregulation the expression level of p-PI3K, p-AKT and retinoic acid receptor α (RARα) and upregulation the expression level of retinoic acid receptor β and γ (RARβ and RARγ). These effects of PI3 kinase inhibitor LY294002 treatment mimicked Berberine treatment except the expression level of RARγ. Moreover, Western blot analysis showed that the decreased PI3K and AKT phosphorylation, increased the epithelial maker E-cadherin, and upregulation level of RARβ while decreased the mesenchymal markers N-cadherin and downregulation level of RARα by incubation with LY294002 in mouse melanoma B16 cells. In conclusion, Our study reveal that berberine can reverse the epithelial to mesenchymal transition of mouse melanoma B16 cells and may be a useful adjuvant therapeutic agent in the treatment of melanoma through the PI3K/Akt pathway and inactivation PI3K/AKT could regulate RARα/RARβ expression.
黄连素是从黄连根茎中提取的一种天然化合物，越来越多的证据表明其具有强大的抗肿瘤特性，对黑色素瘤细胞有多种作用，包括抑制癌细胞活力、阻断细胞周期和迁移。然而，黄连素的作用机制尚未完全阐明。在本研究中，我们发现黄连素降低了B16细胞的迁移和侵袭能力，并显著改变了上皮-间质转化相关因子的多能性。我们发现黄连素还下调了p-PI3K、p-AKT和视黄酸受体α（RARα）的表达水平，并上调了视黄酸受体β和γ（RARβ和RARγ）的表达水平。PI3激酶抑制剂LY294002处理的这些作用除了RARγ的表达水平外，与黄连素处理相似。此外，蛋白质免疫印迹分析表明，在小鼠黑色素瘤B16细胞中用LY294002孵育后，PI3K和AKT磷酸化降低，上皮标志物E-钙黏蛋白增加，RARβ上调，而间充质标志物N-钙黏蛋白降低，RARα下调。总之，我们的研究表明黄连素可以逆转小鼠黑色素瘤B16细胞的上皮-间质转化，并且可能是通过PI3K/Akt途径治疗黑色素瘤的一种有用的辅助治疗剂，使PI3K/AKT失活可以调节RARα/RARβ的表达。
