Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity

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.     

Effects of a specially pulsed electric field on an animal model of wound healing

The possible beneficial effects of a specially pulsed electric field (PEF) on wound healing were investigated in this study. We made a pair of triangular, full-thickness, dorsal incisions in the skin of 32 healthy male mice (one control group and three exposure groups). The treatment groups were kept between parallel plates in a partially insulated exposed environment. Group I was exposed to an electric field intensity of 10 kV/m, group II was exposed to 1.9 kV/m, and group III was exposed to 0.9 kV/m. PEFs were applied to the subjects for 20–22 h and 8 consecutive days. We determined the differences in wound recovery between the groups based on the following parameters: collagen fiber density, inflammatory infiltration density, capillary proliferation, and existence of exudates. We found that a 0.9 kV/m–1.9 kV/m chopped direct current (DC) electric field with a 30 μs repetition time favorably affected collagen synthesis and wound recovery. Despite the intensity of 0.9–1.9 kV/m, PEF accelerated healing, but 10 kV/m decelerated this recovery process.