Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

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

Xi Xia12, Quanfu Ma2, Xiao Li23, Teng Ji2, Pingbo Chen2, Hongbin Xu24, Kezhen Li2, Yong Fang2, Danhui Weng2, Yanjie Weng2, Shujie Liao2, Zhiqiang Han2, Ronghua Liu2, Tao Zhu2, Shixuan Wang2, Gang Xu2, Li Meng2, Jianfeng Zhou2 and Ding Ma2*

Author Affiliations

1 Department of Gynecology & Obstetrics, Nanshan People's Hospital, Guangdong Medical College, Shenzhen, Guangdong, 518052, China

2 Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China

3 Department of Pediatrics, Maternal and Child Health Hospital of Shenzhen, Southern Medical University, Shenzhen, Guangdong, 518038, China

4 Department of Gynecology & Obstetrics, People's Hospital of Shenzhen, Shenzhen, Guangdong, 518020, China

For all author emails, please log on.

BMC Cancer 2011, 11:399  doi:10.1186/1471-2407-11-399

Published: 21 September 2011

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.