Inhibition of COX2 enhances the chemosensitivity of dichloroacetate in cervical cancer cells
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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
Yingru Zheng, email: email@example.com
Fengtian He, email: firstname.lastname@example.org
Keywords: dichloroacetate, COX2, celecoxib, QKI, cervical cancer
Received: February 07, 2017 Accepted: May 06, 2017 Published: June 16, 2017
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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