Open Access

CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells

  • Authors:
    • Fengbin Gao
    • Xiaojing Wang
    • Shanwen Chen
    • Tianyuan Xu
    • Xianjin Wang
    • Yifan Shen
    • Fan Dong
    • Shan Zhong
    • Zhoujun Shen
  • View Affiliations

  • Published online on: August 10, 2018     https://doi.org/10.3892/or.2018.6641
  • Pages: 2445-2454
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Poor response and chemotherapy resistance to cisplatin (DDP)‑based therapy frequently lead to treatment failure in advanced bladder cancer; however the underlying mechanism is extremely complex and unclear. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified human oncoprotein, has been shown to play important regulatory roles in cancer cell survival. The present study aimed to investigate the correlation of CIP2A with sensitivity to DDP in bladder cancer cells. In the present study, knockdown of CIP2A was performed using short hairpin‑RNA. IC50 determination was used to estimate the chemosensitivity of cells to DDP. Apoptosis and DNA damage indicators were tested in vitro and in vivo to clarify the role of CIP2A in enhancing DDP sensitivity. We observed that CIP2A knockdown enhanced DDP sensitivity. CIP2A depletion accelerated the process of DNA damage caused by DDP treatment. Furthermore, DDP triggered inhibition of CIP2A by preventing AKT Ser473 phosphorylation. In vivo, CIP2A suppression increased the cytotoxicity of DDP, which resulted in a decrease in the subcutaneous tumor growth in a xenograft mouse model. Our findings revealed that the mechanism underlying the involvement of CIP2A in DDP sensitivity enhancement is that CIP2A mediates DDP‑induced cell apoptosis and DNA damage. CIP2A is a potential target to improve the response to DDP‑based therapy in bladder cancer patients.
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November-2018
Volume 40 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Gao F, Wang X, Chen S, Xu T, Wang X, Shen Y, Dong F, Zhong S and Shen Z: CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells. Oncol Rep 40: 2445-2454, 2018
APA
Gao, F., Wang, X., Chen, S., Xu, T., Wang, X., Shen, Y. ... Shen, Z. (2018). CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells. Oncology Reports, 40, 2445-2454. https://doi.org/10.3892/or.2018.6641
MLA
Gao, F., Wang, X., Chen, S., Xu, T., Wang, X., Shen, Y., Dong, F., Zhong, S., Shen, Z."CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells". Oncology Reports 40.5 (2018): 2445-2454.
Chicago
Gao, F., Wang, X., Chen, S., Xu, T., Wang, X., Shen, Y., Dong, F., Zhong, S., Shen, Z."CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells". Oncology Reports 40, no. 5 (2018): 2445-2454. https://doi.org/10.3892/or.2018.6641