Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2022; 13:583-584.

Silencing of CXCR4 sensitizes triple-negative breast cancer cells to cisplatin

Sixian Liang _, Xun Peng, Xiaoli Li, Ping Yang, Linhao Xie, Yaochen Li, Caiwen Du and Guojun Zhang

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Oncotarget. 2015; 6:1020-1030. https://doi.org/10.18632/oncotarget.2741

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Abstract

Sixian Liang1,*, Xun Peng2,*, Xiaoli Li1, Ping Yang1, Linhao Xie1, Yaochen Li3, Caiwen Du1, Guojun Zhang3

1Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China

2Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China

3The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515031, PR China

*These two authors contributed equally to this work

Correspondence to:

Caiwen Du, e-mail: dusumc@aliyun.com

Guojun Zhang, e-mail: guoj_zhang@yahoo.com

Keywords: CXCR4, triple-negative breast cancer, cisplatin, chemosensitivity, apoptosis

Received: August 13, 2014     Accepted: November 08, 2014     Published: December 11, 2014

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer for which there is no effective treatment. Previously, we and others demonstrated that CXCR4 surface expression is an independent prognostic factor for disease relapse and survival in breast cancer. In this study, we investigated the effects of CXCR4 gene silencing on cisplatin chemosensitivity in human triple-negative breast cancer cell lines. We found that CXCR4 silencing significantly inhibited cell growth, decreased colony formation, and enhanced cisplatin sensitivity while overexpression of CXCR4 rendered cells more resistant to cisplatin. Moreover, the percentage of apoptosis and cell cycle arrest at the G2/M phase of cisplatin-treated CXCR4 knockdown cells was significantly higher than control cells. Furthermore, we demonstrated CXCR4 knockdown cells showed lower levels of mutant p53 and Bcl-2 protein than the control group, while also having higher levels of caspase-3 and Bax. However overexpression of CXCR4 had the reverse effect. In vivo experiments confirmed that downregulation of CXCR4 enhanced cisplatin anticancer activity in tumor-bearing mice, and that this enhanced anticancer activity is attributable to tumor cell apoptosis. Thus, this study indicates that CXCR4 can modulate cisplatin sensitivity in TNBC cells and suggests that CXCR4 may be a therapeutic target for TNBC.


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