کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525567 1546680 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleMetformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleMetformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis
چکیده انگلیسی


- Metformin is capable of repressing prostate cancer cell migration and invasion as well as castration-induced EMT.
- The repressive effect of metformin on EMT is evidenced by up- and down-regulating epithelial marker and mesenchymal markers.
- Mechanistically, metformin represses EMT of prostate cancer cells by targeting the COX2/PGE2/STAT3 axis.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 389, 28 March 2017, Pages 23-32
نویسندگان
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