The Anti-tumoral Effect of β-D-Mannuronic acid (M2000) as a Novel NSAID on Treg Cells Frequency and MMP-2, MMP-9, CCL22 and TGFβ1 Gene Expression in Breast Cancer Patients

With respect to the role of chronic inflammation in induction and progression of breast cancer (BC), targeting of interaction between tumor and tumor microenvironment may denote a novel hopeful strategy for BC therapy. Regarding the potential positive effect of β-D-Mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) on BC murine model and 4T1 cell line, we started  to study the effects of  M2000 on MMP-2, MMP-9, CCL22 and TGFβ1 gene expression and T regulatory cells (Tregs) frequency in Peripheral Blood Mononuclear Cells (PBMCs) in Iranian women BC patients during 6-8 weeks. The gene expression was evaluated by real-time PCR and the frequency of Tregs were assessed by flow cytometry. Our findings demonstrated that M2000 had valuable therapeutic effects on BC through the reduction in MMP-2, MMP-9, CCL22 and TGFβ1 gene expression and Tregs frequency which play a main role in the development of chronic inflammation, angiogenesis, tumorgenicity and metastasis. whereas no adverse effects were observed following the use of M2000 after 6-8 weeks.

Our findings demonstrated that M2000 therapy as a novel designed NSAID not only inhibits the chronic inflammatory reaction, but also prevents crosstalk between tumor cells and their microenvironment, which is might decline tumor growth and metastasis process.

Clinical Trial Identifier IRCT2017012213739N7/http://www.IRCT.ir.

 

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