Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity
| Autor: | Ercument Ovali, Guven Yenmis, Derya Dilek Kancagi, Nail Besli, Matem Tunçdemir, Elif Yaprak Sarac, Cihan Tastan, Onur Olgac Karagulle, Turgut Ulutin, Kazım Şenol, Tugba Soydas, Muhammet Yilanci, Cumhur Gokhan Ekmekci, Gonul Kanigur Sultuybek |
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| Přispěvatelé: | Tıp Fakültesi |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Histology Immunocytochemistry Antineoplastic Agents Breast Neoplasms Matrix metalloproteinase medicine.disease_cause Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer Breast Cancer medicine Tumor Cells Cultured Humans Neoplasm Invasiveness Viability assay NF-Kb Neoplasm Metastasis MMP-2 business.industry NF-kappa B Cancer Cell Biology General Medicine Middle Aged medicine.disease Metformin Neoplasm Proteins 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Female business Carcinogenesis MMP-9 medicine.drug Signal Transduction |
| Popis: | Current evidence strongly suggests that aberrant activation of the nuclear factor kappa B (NF-kB) signaling cascade is connected to carcinogenesis. The matrix metalloproteinases (MMP) which are also the key agents for tumor metastasis may be potent candidates for tumor diagnosis in clinics. In this in vitro study, we hypothesized that metformin with an effective dose can inhibit tumor cell proliferation and metastasis by modulating the expressions of MMP-2 and -9 and interfering with NF-kB signaling in primary breast cancer cells (PBCCs). 300 000 cells per ml were obtained from biopsies of breast tumors from five human donors. The cell viability and proliferation were tested. Immunocytochemistry was performed for MMP-2, MMP-9, and NF-kB, and enzyme-linked immunosorbent assay for NF-kB activity, quantitative real-time PCR for RELA/p65, IkBα, MMP-2, and MMP-9. Three different doses of metformin (5, 10, and 25 mM) (Met) reduced the viability and proliferation of PBCCs in a dose-dependent manner, maximum inhibition was observed at 25 mM Met. The expression of RELA/p65 was not affected by 25 mM Met. Nuclear immunoreactivity and activity of NF-kB reduced while cytoplasmic NF-kB (p65) elevated by 25 mM Met compared to non-treatment (P < 0.05). The expression and immunoreactivity of MMP-9 but not MMP-2 were decreased by 25 mM Met treatment, compared with the non-treatment (P < 0.05). Metformin may have an essential antitumor role in the invasion and metastasis pathways of PBCCs by downregulating the MMP-9 expression blocking both the activity and nuclear translocation of NF-kB. |
| Databáze: | OpenAIRE |
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