title: 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.affiliation: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, 226001, Nantong, Jiangsu Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Qi
authors.initials: Q
authors.lastname: Qian
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Dandan
authors.initials: D
authors.lastname: Yu
authors.forename: Shiye
authors.initials: S
authors.lastname: Wang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.forename: Dengfu
authors.initials: D
authors.lastname: Yao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D053673:Glypicans / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D034741:RNA, Small Interfering / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D051176:beta Catenin / Q000037:antagonists & inhibitors
chemical_list: D053673:Glypicans; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D007335:Insulin-Like Growth Factor II