1. 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 Pre-surgical Breast Cancer Patients.
- Author
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Kashefi S, Ahmadi H, Omranipour R, Mahmoodzadeh H, Jafarnezhad-Ansariha F, Tofighi Zavareh F, and Mirshafiey A
- Subjects
- Breast Neoplasms drug therapy, Carcinoma, Ductal, Breast drug therapy, Carcinoma, Ductal, Breast genetics, Chemokine CCL22 genetics, Female, Humans, Lymphocyte Count, Matrix Metalloproteinase 2 genetics, Matrix Metalloproteinase 9 genetics, T-Lymphocytes, Regulatory drug effects, Transforming Growth Factor beta1 genetics, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Antineoplastic Agents pharmacology, Breast Neoplasms genetics, Gene Expression Regulation, Neoplastic drug effects, Hexuronic Acids pharmacology
- Abstract
With respect to the role of chronic inflammation in the induction and progression of breast cancer (BC). The relationship between tumor and tumor microenvironment may be a hopeful strategy for BC therapy. According to the 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 that was a phase II, randomized, controlled clinical trial. 24 women with BC were included in this study and were followed by fixed oral doses of M2000, 500 mg two times a day (6-8 weeks). Blood samples were collected at baseline and weeks 6-8. To compare the patterns of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), C-C motif chemokine ligand 22 (CCL22) and The transforming growth factor-beta 1 (TGFβ1) gene expression and T regulatory cells (Tregs) frequency of healthy women normal controls with BC patients, a set of 10 blood samples of women healthy volunteers was collected. The gene expression was evaluated by quantitative Real-time PCR (qRT-PCR) and the frequency of Tregs was assessed by flow cytometry. Our results showed, reduction in MMP-2 (p=0.08), MMP-9 (p=0.03), CCL22 (p=0.003) and TGFβ1 (p=0.1) gene expression and Tregs frequency (p=0.01) which play a main role in the development of chronic inflammation, angiogenesis, tumorigenesis and metastasis. Our findings demonstrated that M2000 therapy as a novel designed NSAID had valuable therapeutic effects on BC. No adverse effects were observed following the use of M2000 after 6-8 weeks.
- Published
- 2019