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.