Clusterin Enhances Cispatin Resistance of Retinoblastoma via Akt Pathway

Abstract

Purpose: : The aim of this study is to investigate the association of clusterin with cisplatin resistance of retinoblastoma.

Methods: : Clusterin expression was evaluated by immunohistochemical staining of clusterin in human retinoblastoma tissue. Cell survival analysis of SNUOT-Rb1 cells was done by MTT assay under various concentrations of cisplatin. Clusterin expression under the treatment of cisplatin was measured by western blot analysis. To evaluate the effect of exogenous clusterin treatment, SNUOT-Rb1 cells were treated with 0.5ug/ml cisplatin in the presence of 10ug/ml clusterin. SNUOT-Rb1 cells transfected with clusterin cDNA underwent MTT assay under the treatment of 0.5 ug/ml cisplatin. The expression of cleaved caspase-3 and phosphorylation status of Akt were measured by western blot analysis in the transfected cells.

Results: : In human retinoblastoma tissue, clusterin was diffusely expressed in the cytoplasm. The expression of clusterin in SNUOT-Rb1 cells increased in a time-dependent manner until 24 h and then decreased. Exogenous clusterin enhanced cisplatin resistance of SNUOT-Rb1 cells. Up-regulation of clusterin by transfection increased cisplatin resistance of SNUOT-Rb1 cells and showed decreased expression of cleaved caspase-3. The transfected cells showed increased expression of phosphorylated Akt.

Conclusions: : High levels of clusterin expression enhance cispatin resistance of retinoblastoma via Akt pathway. Therefore, clusterin is a potential therapeutic target to chemosensitize retinoblastoma to cisplatin.

Keywords: retinoblastoma • tumors • chaperones