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Updated: Mar 9, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Metformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis
Dali Tong1, Qiuli Liu1, Gaolei Liu1
1Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China.
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.
Insights
Metformin inhibits prostate cancer metastasis by repressing epithelial-mesenchymal transition (EMT). This drug targets the COX2/PGE2/STAT3 pathway, offering potential as an anti-metastasis therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Advanced prostate cancer treatment relies on castration but faces challenges with relapse and metastasis.
- Inflammatory signaling and epithelial-mesenchymal transition (EMT) are key drivers of drug resistance, relapse, and metastasis in prostate cancer.
Purpose of the Study:
- To investigate the potential of metformin in inhibiting prostate cancer cell migration and invasion.
- To elucidate the molecular mechanisms by which metformin affects EMT and metastasis.
Main Methods:
- Assessed metformin's effects on prostate cancer cell lines, including migration, invasion, and EMT markers (N-cadherin, Vimentin, Twist, E-cadherin).
- Evaluated metformin's impact on the COX2/PGE2/STAT3 signaling pathway.
- Validated findings in animal models and patient samples.
Main Results:
- Metformin significantly repressed EMT by downregulating mesenchymal markers and upregulating epithelial markers.
- Metformin reduced levels of COX2, PGE2, and phosphorylated STAT3.
- Inactivating COX2 blocked metformin's effects, while PGE2 administration enhanced STAT3 phosphorylation and EMT markers.
Conclusions:
- Metformin inhibits prostate cancer EMT and metastasis by targeting the COX2/PGE2/STAT3 axis.
- Metformin demonstrates potential as a standalone or combination therapy to prevent metastasis in prostate cancer.
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Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...