Targeting Clusterin Induces Apoptosis, Reduces Growth Ability and Invasion and Mediates Sensitivity to Chemotherapy in Human Osteosarcoma Cells

Objective: The aim of the study was to investigate the expression of sCLU in relation to the clinicopathological features and prognosis of patients with untreated High-Grade Osteosarcoma (HGOS) and to evaluate sCLU as a target for osteosarcoma (OS) therapies. Methods: The expression of sCLU in 98 patients of HGOS enrolled from April 2005 to March 2015 at the affiliated hospital of Qingdao University was evaluated by immunohistochemistry. The sCLU expression, clinical data and survival were compared. siRNA-mediated sCLU gene silencing on cell apoptosis, viability, invasion and chemosensitivity to doxorubicin in U2OS cells in vitro was evaluated. Results: sCLU expression was found in 59 (60%) of the 98 patients. A positive correlation was observed between sCLU expression and metastatic disease (P = 0.036) and a negative correlation between sCLU expression and response to chemotherapy (P = 0.002). Targeting sCLU expression in U2OS cells induced significant reduction in cellular growth and higher rates of spontaneous endogenous apoptosis. In addition, targeting sCLU expression inhibited the invasion of U2OS cells. Furthermore, targeting sCLU expression significantly sensitized to chemotherapeutic drug, doxorubicin. Conclusions: The overexpression of sCLU was significantly correlated with metastasis and chemosensitivity in patients with HGOS. sCLU may be a promising therapeutic or chemopreventive target for human OS treatment.