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Tumor Biology

, Volume 35, Issue 6, pp 5857–5868 | Cite as

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

  • Min Yao
  • Li Wang
  • Zhizhen Dong
  • Qi Qian
  • Yun Shi
  • Dandan Yu
  • Shiye Wang
  • Wenjie Zheng
  • Dengfu Yao
Research Article

Abstract

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.

Keywords

Hepatocellular carcinoma Glypican-3 Biological behaviors Targeted therapy Apoptosis 

Abbreviations

EGF

Epidermal growth factor

FQ-RT-PCR

Fluorescence quantitative-reverse transcriptase-PCR

Gli1

Glioma-associated oncogenes 1

GPC-3

Glypican-3

HCC

Hepatocellular carcinoma

Hh

Hedgehogs

IGF

Insulin-like growth factor

shRNA

Short hairpin RNA

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

This work was supported in part by the grants from the Jiangsu Provincial Special Programs of Medical Science (BL2012053, HK201102), the Nantong Undertaking and Technological Innovation (HS2012039), the Post-doctor Funds (2013 M53139, JS2012-468), Chinese National Natural Science Foundation (No.81200634), and the International S&T Cooperation Program (2013DFA32150) of China.

Financial disclosure

None declared.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • 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. 1.Research Center of Clinical MedicineAffiliated Hospital of Nantong UniversityNantongChina
  2. 2.Medical School of Nantong UniversityNantongChina
  3. 3.Department of DiagnosticsAffiliated Hospital of Nantong UniversityNantongChina
  4. 4.Institute of Clinical OncologyAffiliated Hospital of Nantong UniversityNantongChina

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