Tumor-Suppressive Effect of Metformin via the Regulation of M2 Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment of Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture and Reagents
2.2. Flow Cytometry Analysis of M2 Macrophages and MDSCs
2.3. Western Blotting
2.4. ELISA
2.5. In Vivo Experiments Using a Mouse Model of Colorectal Cancer
2.6. Immunohistochemical Staining
2.7. Real-Time PCR
2.8. Statistical Analysis
3. Results
3.1. Metformin, an AMPK Regulator, and Mevalonate Modulate the MDSC and M2 Macrophage Fractions in THP-1 Cells
3.2. Rapamycin and Simvastatin Reduce the MDSC and M2 Macrophage Fractions, an Effect That Is Reversed by Mevalonate Treatment
3.3. Tumor-Suppressive Effects of Metformin in a Mouse Colon Cancer Model
3.4. Metformin Decreases the MDSC and M2 Macrophage Populations by Downregulating the Mevalonate Pathway
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Kang, J.; Lee, D.; Lee, K.J.; Yoon, J.E.; Kwon, J.-H.; Seo, Y.; Kim, J.; Chang, S.Y.; Park, J.; Kang, E.A.; et al. Tumor-Suppressive Effect of Metformin via the Regulation of M2 Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment of Colorectal Cancer. Cancers 2022, 14, 2881. https://doi.org/10.3390/cancers14122881
Kang J, Lee D, Lee KJ, Yoon JE, Kwon J-H, Seo Y, Kim J, Chang SY, Park J, Kang EA, et al. Tumor-Suppressive Effect of Metformin via the Regulation of M2 Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment of Colorectal Cancer. Cancers. 2022; 14(12):2881. https://doi.org/10.3390/cancers14122881
Chicago/Turabian StyleKang, Joyeon, Doyeon Lee, Kyoung Jin Lee, Jaepil Eric Yoon, Ji-Hee Kwon, Yoojeong Seo, Janghyun Kim, Shin Young Chang, Jihye Park, Eun Ae Kang, and et al. 2022. "Tumor-Suppressive Effect of Metformin via the Regulation of M2 Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment of Colorectal Cancer" Cancers 14, no. 12: 2881. https://doi.org/10.3390/cancers14122881