Abstract
Abstract Objective MCF-7 cells, a breast cancer cell line, are used for experiments of estrogen receptor (ER)-positive breast cancer and many sub-clones representing different classes of ER-positive tumors. We aimed to determine the efficacy of metformin, a potential anti-cancer agent, on the cell proliferation, and the expressions of NF-kB (p65), MMP-2 and MMP-9 in MCF-7 cell line. Materials and methods MCF-7 cells (human breast adenocarcinoma) were treated with elevating doses of metformin (0–50 mM) for 24 h. The anti-proliferative effect of metformin was studied by BrdU proliferation assay, and the expression levels of NF-kB (p65), MMP-2 and MMP-9 were analyzed by immunocytochemical staining. Results The percentage of cell proliferation was reduced significantly by 10 and 50 mM doses of metformin (p < 0.001). The expression levels of nuclear NF-kB (p65), MMP-9 and MMP-2 were considerably reduced in 50 mM metformin treated cells while the expression of cytoplasmic NF-kB (p65) elevated compared to control group (p < 0.05). Ten millimolar metformin also reduced expression of MMP-9 significantly (p < 0.05). Conclusion Metformin may act on the proliferation, and the processes of invasion and metastasis of MCF-7 cells through blocking NF-kB, which is intensely expressed in breast cancer cells, and through diminishing the expression of MMP-2 and MMP-9 significantly.
Highlights
Breast cancer, predominantly common in female population worldwide [1], is expressed as a heterogeneous disease with clinical course and its outcome, since it is related to many biological factors that are the nature of the cancer
Alimova et al studied the activity of metformin against diverse molecular subtypes of breast cancer cell lines [MCF-7, MCF-7/713 (MCF-7 transfected with erbB2), BT-474 and SKBR-3] in vitro [25]
The results of NF-kB (p65) immunostaining in the current study indicated that a high dose of metformin increased the expression of cytoplasmic NF-kB (p65) but reduced the nuclear immunostaining for NF-kB in MCF-7 cells significantly, suggesting the inhibition of translocation of both subunits to nucleus (p < 0.05)
Summary
Predominantly common in female population worldwide [1], is expressed as a heterogeneous disease with clinical course and its outcome, since it is related to many biological factors that are the nature of the cancer. The available evidence seems to suggest that understanding this heterogeneity is important in terms of targeted prevention of breast cancer and the biological process that is an obstacle to treatment [2]. Epidemiological studies indicate that women with Type 2 diabetes mellitus (T2DM) may have a tendency to develop breast cancer. A metaanalysis study argues that especially postmenopausal women with T2DM are related to a higher rate in the risk of breast cancer by 23% [3]. On the basis of the epidemic evidence currently available, it seems fair to suggest that the diminished probability of getting cancer in Type 2 diabetic people through metformin uptake becomes widespread in the field of oncology
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