Clusterin Enhances Cisplatin Resistance of Retinoblastoma

Abstract

Purpose: Cisplatin is widely used in various chemotherapy regimens for the treatment of retinoblastoma. Clusterin is cytoprotective chaperone protein that is involved in numerous physiological processes important for tumor growth and carcinogenesis. The expression of clusterin is inversely related with chemosensitivity in several kinds of malignant tumors. 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 blots. To evaluate the effect of exogenous clusterin treatment, SNUOT-Rb1 cells were treated with 1 g/ml cisplatin in the presence of 5 g/ml clusterin. SNUOT-Rb1 cells transfected with clusterin cDNA underwent cell viability assay under the treatment of 1 g/ml cisplatin. The expression of clusterin and cleaved caspase-3 was measured by Western blots.

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 12 h and then decreased. Exogenous clusterin enhanced resistance of SNUOT-Rb1 cells to cisplatin. Upregulation of clusterin by transfection increased cisplatin resistance and showed decreased expression of cleaved caspase-3.

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