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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer

Authors: Xi Xia, Quanfu Ma, Xiao Li, Teng Ji, Pingbo Chen, Hongbin Xu, Kezhen Li, Yong Fang, Danhui Weng, Yanjie Weng, Shujie Liao, Zhiqiang Han, Ronghua Liu, Tao Zhu, Shixuan Wang, Gang Xu, Li Meng, Jianfeng Zhou, Ding Ma

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

P21(WAF1/Cip1) binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer.

Methods

RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry.

Results

p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment.

Conclusions

Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment.
Appendix
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Metadata
Title
Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer
Authors
Xi Xia
Quanfu Ma
Xiao Li
Teng Ji
Pingbo Chen
Hongbin Xu
Kezhen Li
Yong Fang
Danhui Weng
Yanjie Weng
Shujie Liao
Zhiqiang Han
Ronghua Liu
Tao Zhu
Shixuan Wang
Gang Xu
Li Meng
Jianfeng Zhou
Ding Ma
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-399

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