Jian Ma1, Shu-Li Xie1, Ya-Jun Geng1, Shuo Jin1, Guang-Yi Wang2, Guo-Yue Lv3. 1. Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China. 2. Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China. Electronic address: majian10@mails.jlu.edu.cn. 3. Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China. Electronic address: guoyuelv@sina.com.
Abstract
BACKGROUND: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Hae Il Jung; Taesung Ahn; Sang Ho Bae; Jun Chul Chung; Hyungjoo Kim; Susie Chin; Dongjun Jeong; Hyon Doek Cho; Moon Soo Lee; Hyung Chul Kim; Chang Ho Kim; Moo-Jun Baek Journal: Ann Surg Treat Res Date: 2015-01-27 Impact factor: 1.859