ABSTRACT
The aim of this study was to investigate the effects of hirsutine on apoptosis of breast cancer cells and its possible mechanism. The MCF-10A, MCF-7 and MDA-MB-231 cells were treated with hirsutine at different concentrations for 48 h or incubated with 160 μmol/L hirsutine for 24, 48, and 72 h. The MCF-10A cell line is a non-tumorigenic epithelial cell line, and the MCF-7 and MDA-MB-231 are human breast adenocarcinoma cell lines. CCK-8 assay was employed to detect the cell viability. Flow cytometry was used to assay the apoptosis and mitochondrial membrane potential (MMP). The protein expressions of Bcl-2, Bax, cleaved-caspase 9, cleaved-caspase 3 and cytochrome C (Cyt C) in the MDA-MB-231 cells were detected by Western blotting. The results showed that hirsutine remarkably reduced the viability of MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner (P < 0.05) with IC50 values of 447.79 and 179.06 μmol/L, respectively. In the MDA-MB-231 cells, hirsutine induced apoptosis and depolarization of MMP (P < 0.05), released Cyt C from mitochondria (P < 0.05), and activated caspase 9 and caspase 3 (P < 0.05). However, these effects induced by hirsutine were all inhibited by cyclosporin A (CsA) (P < 0.05), a specific inhibitor of mitochondrial permeability transition pore (MPTP). In addition, hirsutine down-regulated the protein level of Bcl-2 and up-regulated the protein level of Bax (P < 0.05). These results suggest that hirsutine may induce apoptosis of human breast cancer MDA-MB-231 cells through decreasing the ratio of Bcl-2 to Bax, opening MPTP, releasing Cyt C from mitochondria, and activating caspase 9 and caspase 3.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the applicability of electrical impedance equipment in assessing local lung volume during different PEEP ventilation and at different respiratory rate in neonatal piglets.</p><p><b>METHODS</b>Electrical impedance measurements (EIM) were performed on 6 healthy newborn piglets (age 4 +/- 1 d, weight 1.66 +/- 0.31 kg) using 8 electrodes distributed to 4 quadrants of the lung (left, right, upper, lower). Tidal impedance and functional residual impedance changes during PEEP levels of 2, 4, 6 and 8 cm H2O and frequencies ranging from 0.5 to 15 Hz were investigated.</p><p><b>RESULTS</b>The sum of regional tidal impedance obtained from four quadrants, significantly reflected tidal volume (VT) measured by a pneumotachograph during both frequency and PEEP changed (r2 = 0.98). A decrease of PEEP 4 to 2 cm H2O caused a significant increase in total tidal impedance (TTI) as well as in VT (P < 0.01 and P < 0.05); whereas an increase in frequency from 0.5 to 15 Hz was associated with a significant decrease in both TTI and VT (P < 0.05 and P < 0.01). Increased frequency had a balancing effect on air distribution, whereas higher PEEP did not result in more homogeneous ventilation. Minimal impedance values (FRI) (surrogate variable for FRC) showed that total FRI significantly decreased with increasing PEEP level.</p><p><b>CONCLUSIONS</b>EIM demonstrated good applicability to assess changes in thoracic gas volume. It is highly suggested that this method could be considered and further studied as a non-invasive bedside method to monitor continuously regional lung ventilation of neonates under any mode of mechanical ventilation.</p>