期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 33, 期 5, 页码 743-751出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.33.743
关键词
HepG2 cell; ouabain; Na+/K+-ATPase; proliferation; cell cycle; small interfering ribonucleic acid
资金
- Science Foundation of Tianjin [06YFJMJC10400]
- National Natural Science Foundation of China [30840010]
Recent research has shown that the Na+/K+-ATPase alpha 1 subunit is a novel anti-cancer target, which plays pivotal roles in malignant cell ion transport, metabolism, migration and signal transduction. The purpose of the present study was to investigate the anti-cancer effects of ouabain and Na+/K+-ATPase alpha 1 small interfering ribonucleic acid (siRNA) on HepG2 cell proliferation, apoptosis and cell cycle, and to explore the molecular mechanisms. The expression of Na+/K+-ATPase alpha 1 subunit in human hepatocellular carcinoma (HCC), normal liver tissues and human HCC line (HepG2, SMMC-7721 and Bel-7402) has been investigated. Using the ouabain and Na+/K+-ATPase alpha 1 subunit siRNA, which target the Na+/K+-ATPase, we have evaluated the effects of inhibiting Na+/K+-ATPase alpha 1 in human HepG2 cells with respect to cell proliferation, morphology, cell cycle, impact on intracellular Ca2+, reactive oxygen species (ROS) concentration, and correlated gene expression level on messenger ribonucleic acid (mRNA) and protein. Our data showed that the expression Na+/K+-ATPase alpha 1 subunit in HCC tissues is higher than that in normal liver tissues. Ouabain and Na+/K+-ATPase alpha 1 siRNA could inhibit HepG2 cell proliferation. Ouabain could induce HepG2 cell apoptosis and generate S phase arrest, and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca2+ and ROS increase-mediated, and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A (P21(CIP1)). We believe that targeting of the Na+/K+-ATPase alpha 1 subunit in human HCC cells could provide new sight into the treatment of HCC.
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