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

// Bo Li 1, * , Xinzhe Li 1, * , Haojun Xiong 1 , Peng Zhou 1 , Zhenhong Ni 1 , Teng Yang 1 , Yan Zhang 1 , Yijun Zeng 1 , Jintao He 2 , Fan Yang 1 , Nan Zhang 1 , Yuting Wang 1 , Yingru Zheng 3 and Fengtian He 1 1 Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China 2 Battalion 17 of Students, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China 3 Department 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.