Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma.

ABSTRACT:

Purpose

Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells.

Methods

The combined effects of OGX-011 and ZOL wer

SUBMITTER: Lamoureux F 

PROVIDER: S-EPMC4202162 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature