Research Papers:
Celecoxib targets breast cancer stem cells by inhibiting the synthesis of prostaglandin E2 and down-regulating the Wnt pathway activity
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Abstract
Chaolin Huang1, Yuanhong Chen1, Hang Liu1, Jing Yang1, Xuejing Song1, Junping Zhao1, Na He1, Chengji J. Zhou2, Yongping Wang2, Changjiang Huang1 and Qiaoxiang Dong1
1Institute of Environmental Safety and Human Health, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, P.R. China
2Department of Biochemistry and Molecular Medicine, University of California at Davis, School of Medicine, Sacramento, CA 95817, USA
Correspondence to:
Qiaoxiang Dong, email: [email protected]
Changjiang Huang, email: [email protected]
Keywords: CSCs; celecoxib; PGE2; Wnt pathway; EMT
Received: June 05, 2017 Accepted: December 03, 2017 Published: December 14, 2017
ABSTRACT
Pharmacological targeting of breast cancer stem cells (CSCs) is highly promising for the treatment of breast cancer, as the small population of CSCs is responsible for tumor initiation, progression, recurrence and chemo-resistance. Celecoxib is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), which have chemo-preventive activity against cancers, including breast cancer and colorectal cancer. However, the mechanisms by which NSAIDs exert its cancer prevention effects have yet been completely understood. In the present study, we investigated for the first time the effect of celecoxib on breast CSCs inhibition and its potential molecular mechanisms. Our results demonstrated that celecoxib suppresses CSC self-renewal, sensitizes chemo-resistance, inhibits epithelial to mesenchymal transition (EMT), and attenuates metastasis and tumorigenesis. Further exploring the underlying mechanism revealed that celecoxib targets breast CSCs by inhibiting the synthesis of prostaglandin E2 and down-regulating the Wnt pathway activity. Our findings suggest that celecoxib, by targeting CSCs, may be used as an adjuvant chemotherapy drug to improve breast cancer treatment outcomes.

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