Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China.
Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China.
Clin Res Hepatol Gastroenterol. 2014 Feb;38(1):73-80. doi: 10.1016/j.clinre.2013.06.012. Epub 2013 Jul 30.
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and is characterized by advanced clinical stages at diagnosis and very poor prognosis.
This study investigated the effects of PI3K inhibitor, LY294002, on suppression of astrocyte elevated gene-1 (AEG-1) and regulation of HCC cell viability, apoptosis, and invasion in vitro. Cell lines derived from normal liver and HCC were treated with LY294002 and evaluated by RT-PCR, western blot, cell viability, migration, and invasion assays.
The data showed that AEG-1 mRNA and protein were overexpressed in HCC cells, compared to the normal liver cells. LY294002 treatment of HCC cells significantly reduced tumor cell viability, but promoted apoptosis. Tumor cell migration and invasion assays showed that LY294002 treatment also decreased the capacity of HCC cell migration and invasion. Molecularly, LY294002 treatment down-regulated AEG-1 expression, AKT and GSK3β phosphorylation, and expression of cyclinD1, CDK4, VEGF and Bcl2, but up-regulated Bax and c-Myc expression.
The data from this study demonstrated usefulness of LY294002 for effective control of HCC. Future studies should investigate the effects of LY294002 on HCC cells in vivo before initiating clinical trials in HCC patients.
肝细胞癌（HCC）是世界上最常见的恶性肿瘤之一，其特点是在诊断时已处于晚期临床阶段，预后极差。
本研究探讨了 PI3K 抑制剂 LY294002 对体外抑制星形细胞上调基因-1（AEG-1）和调节肝癌细胞活力、凋亡和侵袭的影响。用 LY294002 处理源自正常肝脏和 HCC 的细胞系，并通过 RT-PCR、western blot、细胞活力、迁移和侵袭实验进行评估。
数据显示，与正常肝细胞相比，AEG-1mRNA 和蛋白在 HCC 细胞中过度表达。LY294002 处理 HCC 细胞可显著降低肿瘤细胞活力，但促进凋亡。肿瘤细胞迁移和侵袭实验表明，LY294002 处理还降低了 HCC 细胞迁移和侵袭的能力。分子水平上，LY294002 处理下调了 AEG-1 表达、AKT 和 GSK3β 磷酸化以及细胞周期蛋白 D1、CDK4、VEGF 和 Bcl2 的表达，但上调了 Bax 和 c-Myc 的表达。
本研究数据表明，LY294002 可有效控制 HCC。未来的研究应在 HCC 患者开始临床试验之前，研究 LY294002 对 HCC 细胞的体内作用。
