Abstract

Purpose: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an identified human oncoprotein which modulates malignant cell growth. It is overexpressed in human prostate cancer and in most of the human malignancies. The aim of this study was to investigate the effects of CIP2A silencing on the sensitivity of PC-3 prostate cancer cells to docetaxel chemotherapy.Methods: PC-3 cells were transfected using CIP2A siRNA. CIP2A mRNA and protein expression were assessed after CIP2A gene silencing using q-RT PCR and Western blotting. Proliferation and apoptosis were analyzed after treatment with docetaxol using MTT assay, DAPI staining, and flow cytometry, respectively.Results: Silencing of CIP2A enhanced the sensitivity of PC-3 cells to docetaxel by strengthening docetaxel induced cell growth inhibition and apoptosis against PC-3 cells.Conclusion: Silencing of CIP2A may potentiate the cytotoxic effects of docetaxel and this might be a promising therapeutic approach in prostate cancer treatment.

Highlights

  • Prostate cancer is the common malignancy among men and it accounts for the second cause of cancer-related death in men.[1,2] In spite of significant efforts in the treatment of prostate cancer, conventional therapies could not successfully treat the tumors

  • The effect of Cancerous inhibitor of protein phosphatase 2A (CIP2A) suppression on docetaxel induced cytotoxicity against prostate cancer cells has not been reported, this study investigated the effects of CIP2A silencing on the sensitivity of PC-3 cells to docetaxel chemotherapy

  • CIP2A siRNA down-regulated CIP2A expression in PC-3 cells To investigate the effect of CIP2A siRNA on CIP2A expression in PC-3 cells, the CIP2A expression in PC-3 cells was knocked down by specific CIP2A siRNA for 24, 48, and 72 h with 60 pmol of CIP2A siRNA

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Summary

Introduction

Prostate cancer is the common malignancy among men and it accounts for the second cause of cancer-related death in men.[1,2] In spite of significant efforts in the treatment of prostate cancer, conventional therapies could not successfully treat the tumors. Cancerous inhibitor of protein phosphatase 2A (CIP2A), a human oncoprotein, is generally overexpressed in most human malignancies and its overexpression is closely associated with poor outcome in patients.[13,14] It promotes malignant cell growth and tumor progression.[15] It is overexpressed in prostate cancer samples and cell lines.[16,17] Since, the effect of CIP2A suppression on docetaxel induced cytotoxicity against prostate cancer cells has not been reported, this study investigated the effects of CIP2A silencing on the sensitivity of PC-3 cells to docetaxel chemotherapy

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