Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California (UCLA), Los Angeles, CA 90095-1781, USA.
Laboratory of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Nagoya 468-8503, Japan.
Oncol Rep. 2018 Jun;39(6):2924-2930. doi: 10.3892/or.2018.6357. Epub 2018 Apr 5.
Regucalcin, which its gene is localized on the X chromosome, plays a pivotal role as a suppressor protein in signal transduction in various types of cells and tissues. Regucalcin gene expression has been demonstrated to be suppressed in various tumor tissues of animal and human subjects, suggesting a potential role of regucalcin in carcinogenesis. Regucalcin, which is produced from the tissues including liver, is found to be present in the serum of human subjects and animals. This study was undertaken to determine the effects of exogenous regucalcin on the proliferation in cloned human hepatoma HepG2 cells in vitro. Proliferation of HepG2 cells was suppressed after culture with addition of regucalcin (0.01 – 10 nM) into culture medium. Exogenous regucalcin did not reveal apoptotic cell death in HepG2 cells in vitro. Suppressive effects of regucalcin on cell proliferation were not enhanced in the presence of various signaling inhibitors including tumor necrosis factor-α (TNF-α), Bay K 8644, PD98059, staurosporine, worthomannin, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) or gemcitabine, which were found to suppress the proliferation. In addition, exogenous regucalcin suppressed the formation of colonies of cultured hepatoma cells in vitro. These findings demonstrated that exogenous regucalcin exhibits a suppressive effect on the growth of human hepatoma HepG2 cells, proposing a strategy with the gene therapy for cancer treatment.
Regucalcin 是一种位于 X 染色体上的基因，作为一种信号转导的抑制蛋白，在各种类型的细胞和组织中发挥着关键作用。已经证明，Regucalcin 基因在动物和人类的各种肿瘤组织中受到抑制，提示 Regucalcin 在肿瘤发生中可能发挥作用。Regucalcin 由包括肝脏在内的组织产生，在人类和动物的血清中被发现存在。本研究旨在确定外源性 Regucalcin 对体外克隆人肝癌 HepG2 细胞增殖的影响。在培养基中加入 Regucalcin（0.01 至 10 nM）培养后，HepG2 细胞的增殖受到抑制。外源性 Regucalcin 未在体外 HepG2 细胞中显示凋亡性细胞死亡。Regucalcin 对细胞增殖的抑制作用在存在各种信号抑制剂（包括肿瘤坏死因子-α（TNF-α）、Bay K 8644、PD98059、staurosporine、wortmannin、5,6-二氯-1-β-D-核糖呋喃基苯并咪唑（DRB）或吉西他滨）时并未增强，这些抑制剂被发现可抑制细胞增殖。此外，外源性 Regucalcin 抑制体外培养肝癌细胞集落的形成。这些发现表明，外源性 Regucalcin 对人肝癌 HepG2 细胞的生长具有抑制作用，为癌症治疗的基因治疗策略提供了依据。
