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Cancer Lett. 2017 Mar 28;389:23-32. doi: 10.1016/j.canlet.2016.12.031. Epub 2016 Dec 30.

Metformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis.

Author information

1
Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China.
2
Department of Pathology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China.
3
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA 19131, USA.
4
Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China. Electronic address: jiangjun_64@163.com.

Abstract

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.

KEYWORDS:

EMT; Metformin; Prostate cancer

PMID:
28043910
DOI:
10.1016/j.canlet.2016.12.031
[Indexed for MEDLINE]

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