Oncotarget

Research Papers:

Inhibition of COX2 enhances the chemosensitivity of dichloroacetate in cervical cancer cells

Bo Li, Xinzhe Li, Haojun Xiong, Peng Zhou, Zhenhong Ni, Teng Yang, Yan Zhang, Yijun Zeng, Jintao He, Fan Yang, Nan Zhang, Yuting Wang, Yingru Zheng _ and Fengtian He

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Oncotarget. 2017; 8:51748-51757. https://doi.org/10.18632/oncotarget.18518

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Abstract

Bo Li1,*, Xinzhe Li1,*, Haojun Xiong1, Peng Zhou1, Zhenhong Ni1, Teng Yang1, Yan Zhang1, Yijun Zeng1, Jintao He2, Fan Yang1, Nan Zhang1, Yuting Wang1, Yingru Zheng3 and Fengtian He1

1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China

2Battalion 17 of Students, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China

3Department of Obstetrics and Gynecology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China

*These authors have contributed equally to this work

Correspondence to:

Yingru Zheng, email: zyrdaping@aliyun.com

Fengtian He, email: hefengtian06@aliyun.com

Keywords: dichloroacetate, COX2, celecoxib, QKI, cervical cancer

Received: February 07, 2017     Accepted: May 06, 2017     Published: June 16, 2017

ABSTRACT

Dichloroacetate (DCA), a traditional mitochondria-targeting agent, has shown promising prospect as a sensitizer in fighting against malignancies including cervical cancer. But it is unclear about the effect of DCA alone on cervical tumor. Moreover, previous reports have demonstrated that the increased cyclooxygenase-2 (COX2) expression is associated with chemoresistance and poor prognosis of cervical cancer. However, it is still unknown whether COX2 can affect the sensitivity of DCA in cervical cancer cells. In this study, we found that cervical cancer cells were insensitive to DCA. Furthermore, we for the first time revealed that DCA could upregulate COX2 which impeded the chemosensitivity of DCA in cervical cancer cells. Mechanistic study showed that DCA reduced the level of RNA binding protein quaking (QKI), leading to the decay suppression of COX2 mRNA and the subsequent elevation of COX2 protein. Inhibition of COX2 using celecoxib could sensitize DCA in repressing the growth of cervical cancer cells both in vitro and in vivo. These results indicate that COX2 is a novel resistance factor of DCA, and combination of celecoxib with DCA may be beneficial to the treatment of cervical cancer.


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