Feng Xiao-Yi, Zhao Wei, Yao Zheng, Wei Ning-Yi, Shi An-Hua, Chen Wen-Hui
Faculty of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, China.
Front Pharmacol. 2021 Oct 7;12:720368. doi: 10.3389/fphar.2021.720368. eCollection 2021.
The Na/K-ATPase α1 subunit (ATP1A1) is a potential target for hepatic carcinoma (HCC) treatment, which plays a key role in Na/K exchange, metabolism, signal transduction, etc. , we found that saponins (PNS) could inhibit tumor growth and significantly downregulate the expression and phosphorylation of ATP1A1/AKT/ERK in tumor-bearing mice. Our study aims to explore the potential effects of PNS on the regulation of ATP1A1 and the possible mechanisms of antitumor activity. The effects of PNS on HepG2 cell viability, migration, and apoptosis were examined . Fluorescence, Western blot, and RT-PCR analyses were used to examine the protein and gene expression. Further analysis was assessed with a Na/K-ATPase inhibitor (digitonin) and sorafenib . We found that the ATP1A1 expression was markedly higher in HepG2 cells than in L02 cells and PNS exhibited a dose-dependent effect on the expression of ATP1A and the regulation of AKT/ERK signaling pathways. Digitonin did not affect the expression of ATP1A1 but attenuated the effects of PNS on the regulation of ATP1A1/AKT/ERK signaling pathways and enhanced the antitumor effect of PNS by promoting nuclear fragmentation. Taken together, PNS inhibited the proliferation of HepG2 cells downregulation of ATP1A1 and signal transduction. Our findings will aid a data basis for the clinical use of PNS.
钠钾ATP酶α1亚基（ATP1A1）是肝癌（HCC）治疗的潜在靶点，其在钠钾交换、代谢、信号转导等过程中起关键作用。我们发现人参皂苷（PNS）可抑制荷瘤小鼠肿瘤生长，并显著下调ATP1A1/AKT/ERK的表达及磷酸化水平。本研究旨在探讨PNS对ATP1A1调控的潜在作用及抗肿瘤活性的可能机制。检测了PNS对HepG2细胞活力、迁移和凋亡的影响。采用荧光、蛋白质免疫印迹和逆转录-聚合酶链反应分析检测蛋白质和基因表达。使用钠钾ATP酶抑制剂（洋地黄皂苷）和索拉非尼进行进一步分析。我们发现，HepG2细胞中ATP1A1的表达明显高于L02细胞，PNS对ATP1A的表达及AKT/ERK信号通路的调控呈剂量依赖性作用。洋地黄皂苷不影响ATP1A1的表达，但减弱了PNS对ATP1A1/AKT/ERK信号通路调控的作用，并通过促进核碎裂增强了PNS的抗肿瘤作用。综上所述，PNS通过下调ATP1A1和信号转导抑制HepG2细胞增殖。我们的研究结果将为PNS的临床应用提供数据基础。
