Journal
CANCER LETTERS
Volume 389, Issue -, Pages 23-32Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.12.031
Keywords
Prostate cancer; Metformin; EMT
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81172442, 81402120]
- Chongqing Science and Technology Commission [2011GZ0047]
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Castration is the standard therapeutic treatment for advanced prostate cancer but with limited benefit due to the profound relapse and metastasis. Activation of inflammatory signaling pathway and initiation of epithelial mesenchymal transition (EMT) are closely related to drug resistance, tumor relapseas well as metastasis. In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin. These effects have also been observed in our animal model as well as prostate cancer patients. In addition, we showed the effects of metformin on the expression of genes involved in EMT through repressing the levels of COX2, PGE2 and phosphorylated STAT3. Furthermore, inactivating COX2 abolishes metformin's regulatory effects and exogenously administered PGE2 is capable of enhancing STAT3 phosphorylation and expression of EMT biomarker. We propose that metformin represses prostate cancer EMT and metastasis through targeting the COX2/PGE2/STAT3 axis. These findings suggest that metformin by itself or in combination with other anticancer drugs could be used as an anti-metastasis therapy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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