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

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.

• Authors: Min Yao, Li Wang, Zhizhen Dong, Qi Qian, Yun Shi, Dandan Yu, Shiye Wang, Wenjie Zheng, Dengfu Yao
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 6 Pg. 5857-68 (Jun 2014) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 24633918 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glypicans
• RNA, Small Interfering
• Vascular Endothelial Growth Factor A
• beta Catenin
• Insulin-Like Growth Factor II

Topics

• Carcinoma, Hepatocellular (pathology, therapy)
• Genetic Therapy
• Glypicans (antagonists & inhibitors, genetics)
• Humans
• Insulin-Like Growth Factor II (genetics)
• Liver Neoplasms (pathology, therapy)
• Molecular Targeted Therapy
• RNA, Small Interfering (genetics)
• Vascular Endothelial Growth Factor A (genetics)
• beta Catenin (antagonists & inhibitors)