CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
|---|---|
| Enthalten in: |
Oncology reports - 40(2018), 5 vom: 28. Nov., Seite 2445-2454 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gao, Fengbin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.11.2018 Date Revised 10.12.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.3892/or.2018.6641 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM28745052X |
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| 245 | 1 | 0 | |a CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells |
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| 520 | |a 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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| 700 | 1 | |a Chen, Shanwen |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Tianyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xianjin |e verfasserin |4 aut | |
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| 700 | 1 | |a Dong, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Zhoujun |e verfasserin |4 aut | |
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