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钠钾ATP酶α1亚基，一种新型的肝细胞癌治疗靶点。

Na+/K+-ATPase α1 subunit, a novel therapeutic target for hepatocellular carcinoma.

作者信息

Zhuang Liping, Xu Litao, Wang Peng, Jiang Yan, Yong Pan, Zhang Chenyue, Zhang Haibin, Meng Zhiqiang, Yang Peiying

机构信息

Department of Integrative Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Collaborative Innovation Center for Cancer Medcine, Shanghai, China.

Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

Oncotarget. 2015 Sep 29;6(29):28183-93. doi: 10.18632/oncotarget.4726.

DOI:10.18632/oncotarget.4726
PMID:26334094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4695053/
Abstract

We aimed to identify the expression patterns of Na+/K+-ATPase (NKA) α subunits in human hepatocellular carcinoma (HCC) samples and evaluate these subunits as potential targets for HCC treatment. The mRNA expression profiles of NKA α subunits in human HCC samples were analyzed. We found that the mRNA expression for NKA α1 subunit (ATP1A1) was higher than that for other NKA α subunits. Also, ATP1A1 gene expression was markedly higher in HCC samples than in adjacent nontumor tissue samples. Western blotting data suggested that 6 of 14 (43%) HCC samples had elevated ATP1A1 protein expression. Furthermore, knockdown of ATP1A1 expression in human HCC HepG2 and MHCC97H cells markedly reduced their proliferation in vitro and suppressed the tumorigenicity of MHCC97H cells in vivo. Downregulation of ATP1A1 expression resulted in cell-cycle arrest at G2/M phase and apoptosis in HepG2 cells as well as decreased migration in Hep3B cells. We further validated that ATP1A1 downregulation caused intracellular accumulation of reactive oxygen species. Pretreatment with N-acetyl cysteine blocked cell-growth inhibition induced by ATP1A1 downregulation. Collectively, these data suggested that targeting ATP1A1 is a novel approach to the treatment of HCC.

摘要

我们旨在确定钠钾ATP酶（NKA）α亚基在人肝细胞癌（HCC）样本中的表达模式，并评估这些亚基作为HCC治疗潜在靶点的可能性。分析了人HCC样本中NKA α亚基的mRNA表达谱。我们发现NKA α1亚基（ATP1A1）的mRNA表达高于其他NKA α亚基。此外，ATP1A1基因在HCC样本中的表达明显高于相邻的非肿瘤组织样本。蛋白质印迹数据表明，14例HCC样本中有6例（43%）ATP1A1蛋白表达升高。此外，敲低人HCC HepG2和MHCC97H细胞中ATP1A1的表达显著降低了它们在体外的增殖，并抑制了MHCC97H细胞在体内的致瘤性。ATP1A1表达下调导致HepG2细胞在G2/M期细胞周期阻滞和凋亡，并导致Hep3B细胞迁移减少。我们进一步证实，ATP1A1下调导致细胞内活性氧积累。用N-乙酰半胱氨酸预处理可阻断ATP1A1下调诱导的细胞生长抑制。总的来说，这些数据表明靶向ATP1A1是一种治疗HCC的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/56c93fc393f3/oncotarget-06-28183-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/92e2f327b6a2/oncotarget-06-28183-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/cadb90a6716a/oncotarget-06-28183-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/6fbb8ea12033/oncotarget-06-28183-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/56c93fc393f3/oncotarget-06-28183-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/92e2f327b6a2/oncotarget-06-28183-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/4446bba099c7/oncotarget-06-28183-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/cadb90a6716a/oncotarget-06-28183-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/a62683734d03/oncotarget-06-28183-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/4695053/6fbb8ea12033/oncotarget-06-28183-g005.jpg
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