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, Dengfu Yao*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 20 , 2020

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Abstract:

Background: Although secretory clusterin (sCLU) plays a crucial role in Hepatocellular Carcinoma (HCC) cells proliferation, Multiple Drug Resistance (MDR), metastasis and so on, its targeted effects and exact mechanism are still unknown. This review summarizes some new progress in sCLU as a molecular-targeted therapy in the treatment of HCC.

Methods: A systematic review of the published English-language literature about sCLU and HCC has been performed using the PubMed and bibliographic databases. Some valuable studies on 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 the positive rate of sCLU was significantly higher in HCC tissues as compared to the surrounding tissues at mRNA or protein level, gradually increasing with tumor-nodemetastasis staging (P<0.05). Also, the 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 cancer cell proliferation with an increase in apoptosis, cell cycle arrest, reversal MDR, alteration of cell migration or invasion behaviors, and a decrease in GSK-3β or AKT phosphorylation in vitro, as well as significant suppression of the xenograft growth by down-regulating β-catenin, p-GSK3β, and cyclinD1 expression in vivo.

Conclusion: Abnormal hepatic sCLU expression should not only be 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.

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