Na+/K+-ATPase α3 mediates sensitivity of hepatocellular carcinoma cells to bufalin
Na+/K+-ATPase α3 mediates sensitivity of hepatocellular carcinoma cells to bufalin
复制标题
DOI：
10.3892/or.2010.1120
复制
发表时间：
2011-03-01
期刊：
影响因子：
4.2
通讯作者：
Yang, Peying
中科院分区：
文献类型：
--
作者：
Li, Huaxing;Wang, Peng;Yang, Peying
蟾毒灵是中药蟾酥的主要活性成分，对多种肿瘤细胞具有显著的抗肿瘤活性。然而，确切的机制仍不清楚。本研究证实蟾蜍灵对肝癌细胞的生长具有剂量依赖性的抑制作用，并与Na+/K+-ATP酶α 3的表达水平相关。RNA干扰沉默Na ~+/K ~+-ATP酶α_3后，蟾蜍灵的IC_（50）明显增加。此外，我们发现蟾毒灵增加Akt和ERK 1/2的磷酸化，同时抑制FoxO 3a的表达。因此，我们的研究表明，Na+/K+-ATP酶α 3可能作为蟾蜍灵在HCC中的治疗靶点，其表达状态可能有助于预测HCC细胞对蟾蜍灵治疗的敏感性。
Bufalin, a major bioactive component of the Chinese medicine Chansu, has been reported to exhibit significant antitumor activity against various cancer cell lines. However, the exact mechanism remains unclear. In this study, we demonstrated that bufalin inhibited the growth of hepatocellular carcinoma (HCC) cells in a dose-dependent manner, which correlated with the expression level of Na+/K+-ATPase alpha 3 in HCC cells. The IC50 of bufalin markedly increased when Na+/K+-ATPase alpha 3 was silenced by RNA interference. Furthermore, we show that bufalin increased the phosphorylation of Akt and ERK1/2 while inhibited FoxO3a expression. Thus, our study suggests that Na+/K+-ATPase alpha 3 might serve as a therapeutic target for bufalin in HCC, and its expression status may help predict sensitivity of HCC cells to bufalin treatment.