Down-regulating Glypican-3 Expression: Molecular-targeted Therapy for Hepatocellular Carcinoma

Author(s): Zhizhen Dong , Min Yao , Li Wang , Junling Yang , Dengfu Yao .

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 14 , Issue 14 , 2014

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Abstract:

Hepatocellular carcinoma (HCC) prognosis is very poor, its early treatment is of the utmost importance. Glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, plays a crucial role in cell proliferation and metastasis, particularly in progression. GPC-3 mediated oncogenesis involves signaling pathways during the malignant transformation of hepatocyte carcinogenesis, with an increasing expression of GPC-3 observed from non-cancerous- to cancerous-tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. GPC-3 expression in HCC tissues or circulating blood was associated with tumor size or HBV infection. Circulation of GPC-3-mRNA was detected in HCC patients with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis. After hepatoma, cells were transfected with shRNA, GPC-3 expression or proliferation was inhibited with promoting apoptosis, cell cycle arrested in G1 phase, alteration of hepatoma cell migration and invasion behaviors with down-regulation of β-catenin, IGF-II, and VEGF, and growth of nude mice xenograft tumors was significantly suppressed with the decreases in β -catenin, p-GSK3β, and cyclinD1 expression, suggesting that GPC-3 not only is a specific biomarker for HCC diagnosis, but also is a valuable molecular-target for HCC gene therapy.

Keywords: Diagnosis, glypican-3, hepatocellular carcinoma, signal pathways, targeted-therapy.

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Article Details

VOLUME: 14
ISSUE: 14
Year: 2014
Page: [1183 - 1193]
Pages: 11
DOI: 10.2174/1389557515666150101105135
Price: $58

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