Glypican-3 as an emerging molecular target for hepatocellular carcinoma gene therapy

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• 作者：Min Yao (1)
  Li Wang (2)
  Zhizhen Dong (3)
  Qi Qian (4)
  Yun Shi (4)
  Dandan Yu (4)
  Shiye Wang (4)
  Wenjie Zheng (1)
  Dengfu Yao (1)
  
• 关键词：Hepatocellular carcinoma ; Glypican ; 3 ; Biological behaviors ; Targeted therapy ; Apoptosis
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：35
• 期：6
• 页码：5857-5868
• 全文大小：
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• 作者单位：Min Yao (1)
  Li Wang (2)
  Zhizhen Dong (3)
  Qi Qian (4)
  Yun Shi (4)
  Dandan Yu (4)
  Shiye Wang (4)
  Wenjie Zheng (1)
  Dengfu Yao (1)
  
  1. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, 226001, Nantong, Jiangsu Province, China
  2. Medical School of Nantong University, 19 Qixiu Road, 226001, Nantong, Jiangsu Province, China
  3. Department of Diagnostics, Affiliated Hospital of Nantong University, 20 West Temple Road, 226001, Nantong, Jiangsu Province, China
  4. Institute of Clinical Oncology, Affiliated Hospital of Nantong University, 20 West Temple Road, 226001, Nantong, Jiangsu Province, China
  
• ISSN：1423-0380

文摘

Glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, plays a crucial role in cell proliferation and metastasis, particularly in hepatocellular carcinoma (HCC) progression, and perhaps is a valuable target for its gene therapy. However, its mechanism remains to be explored. In the present study, the biological behaviors of HCC cells were investigated by interfering GPC-3 gene transcription. After the cells were transfected with specific GPC-3 short hairpin RNA (shRNA), the inhibition of GPC-3 expression was 75.6?% in MHCC-97H or 73.8?% in Huh7 cells at mRNA level; the rates of proliferation and apoptosis were 53.6 and 60.5?% in MHCC-97H or 54.9 and 54.4?% in Huh7 cells, with the cell cycles arrested in the G1 phase; the incidences of cell migration, metastasis, and invasion inhibition were 80.1, 56.4, and 69.1?% in MHCC-97H or 80.9, 59.6, and 58.3?% in Huh7 cells, respectively. The cell biological behaviors were altered by silencing GPC-3 with down-regulation of β-catenin, insulin-like growth factor-II and vascular endothelial growth factor, and Gli1 up-regulation. The cell proliferation was significantly inhibited (up to 95.11?%) by shRNA plus anti-cancer drugs, suggesting that GPC-3 gene should be a potential target for promoting hepatoma cell apoptosis and inhibiting metastasis through the Wnt/β-catenin and Hh singling pathways.