Therapeutic role of meloxicam targeting secretory clusterin-mediated invasion in hepatocellular carcinoma cells

Abstract

Recurrence and metastasis are the two leading causes of poor prognosis in patients with hepatocellular carcinoma (HCC). Secreted clusterin (sCLU) is a stress-induced chaperone that is overexpressed in HCC. However, the precise molecular mechanisms of sCLU in HCC invasion and migration are largely unknown. In the present study, it was indicated that downregulation of sCLU significantly alleviated invasiveness whereas overexpression of sCLU notably enhanced the number of invasive cells via mediating the expression level of MMP-2 and E-cadherin in Bel-7402 and SMMC-7721 cells. Furthermore, as an important mediator of invasiveness, sCLU may be responsible for proliferation and invasion suppression induced by meloxicam (a selective inhibitor of cyclooxygenase-2) in HCC cells. The combination of meloxicam and CLU shRNA significantly decreased invasion in HCC cells in vitro. Furthermore, it was observed that overexpression of sCLU significantly potentiated expression of p-AKT and MMP-2. However, downregulation of sCLU by CLU shRNA alleviated the extent of p-AKT. These results suggest the targeting of sCLU may be a novel therapeutic strategy against invasion and migration in HCC.