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Secretory Clusterin As A Novel Molecular-targeted Therapy for Inhibiting Hepatocellular Carcinoma Growth

Author(s):

Min Yao*, Wenli Sai*, Wenjie Zheng, Li Wang, Zhizhen Dong and Dengfu Yao   Pages 1 - 11 ( 11 )

Abstract:


Background: Although secretory clusterin (sCLU) plays a crucial role in hepatocellular carcinoma (HCC) cells proliferation, multiple drug resistance (MDR), metastasis, and so on. However, its targeted-effects and exact mechanisms are still unknown. This review summarizes some new progress of sCLU as molecular-targeted in treatment of HCC.

Methods: A systematic review of the published English-language literatures about sCLU and HCC has been performed using the PubMed or bibliographic databases. Some valuable studies of sCLU in HCC progression were searched for relevant articles with the keywords: HCC, diagnosis, MDR, as molecular-targeted in treatment, and so on.

Results: The incidence of sCLU positive rate was significantly higher in HCC tissues more than that in their surrounding tissues at mRNA or protein level, gradually increasing with tumor-node-metastasis staging (P<0.05). Also, abnormal level of sCLU was related to poor differentiation degree, and considered as a useful marker for HCC diagnosis or independent prognosis for patients. Hepatic sCLU could be silenced at mRNA level by specific sCLU-shRNA or by OGX-011 to inhibit cancerous cell proliferation with apoptosis increasing, cell cycle arrested, reversal MDR, alteration of cell migration or invasion behaviors, and decreasing GSK-3β or AKT phosphorylation in vitro, and significantly suppressed the xenograft growth by down-regulating β-catenin, p-GSK3β, and cyclinD1 expression in vivo.

Conclusion: Abnormal hepatic sCLU expression should be not only a new diagnostic biomarker but also a novel promising target for inhibiting HCC growth.

Keywords:

Hepatocellular carcinoma (HCC), Secretory clusterin (sCLU), Targeted- therapy, Diagnosis, Prognosis, Hepatocarcinogenesis

Affiliation:

Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province



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