RESUMEN
<p><b>OBJECTIVE</b>To explore the roles of NF-κB in factor VIIa-induced proliferation and migration of a colon cancer cell line (SW620) in vitro and its possible mechanism.</p><p><b>METHODS</b>The expression levels of NF-κB (p65), inhibitory protein of NF-κB (IκB-α), caspase-7, interleukin 8 (IL-8) and tissue factor (TF) in SW620 cells treated with factor VIIa, PDTC (an inhibitor of NF-κB) and other factors were measured by Western-blotting and real-time PCR. Proliferation and migration of the cells were analyzed by flow cytometry and Transwell assay, respectively.</p><p><b>RESULTS</b>Factor VIIa down-regulated the IκB-α level in SW620 cells and increased the intranuclear level of NF-κB. Those effects of factor VIIa were blocked by anti-TF or anti-PAR2 antibodies. The effects of factor VIIa on proliferation and migration of SW620 cells, expression of IL-8, TF as well as caspase-7, were interfered by PDTC (the inhibitor of NF-κB).</p><p><b>CONCLUSIONS</b>TF/VIIa complex activates NF-κB pathway via PAR2, thereby up-regulates IL-8 and down-regulates caspase-7 expression in SW620 cells, finally promotes proliferation and migration of colon cancer cells. In addition, TF/VIIa/PAR2/NF-κB pathway also upregulates TF expression, thus to create a positive feedback loop of TF/VIIa/PAR2/NF-κB/TF.</p>
Asunto(s)
Humanos , Antineoplásicos , Farmacología , Caspasa 7 , Genética , Metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias del Colon , Metabolismo , Patología , Factor VIIa , Farmacología , Proteínas I-kappa B , Metabolismo , Interleucina-8 , Genética , Metabolismo , Inhibidor NF-kappaB alfa , Prolina , Farmacología , ARN Mensajero , Metabolismo , Receptor PAR-2 , Metabolismo , Tiocarbamatos , Farmacología , Tromboplastina , Genética , Metabolismo , Factor de Transcripción ReIA , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes.</p><p><b>METHODS</b>Healthy rabbits (1.6-1.8 kg) were treated with amiodarone (80 mg x kg(-1) x d(-1)) for four weeks. Action potential duration (APD) was recorded under isolated arterially perfused left ventricular wedge preparation, then single myocytes were isolated using enzyme digestion. L-type calcium current recovery (time constant, tau) were determined by fitting data with monoexponential. Tau/APD90 were compared in cells treated with saline, amiodarone and sotalol (3 x 10(-5) mmol/L).</p><p><b>RESULTS</b>In chronic amiodarone treated myocytes, tau [(164 +/- 8) ms vs. (98 +/- 8) ms, P<0.05], APD90 [(321 +/- 12) ms vs. (220 +/- 10) ms, P<0.05] and tau/APD90 (0.51 +/- 0.03 vs. 0.44 +/- 0.03, P<0.05) were significantly increased than those in control myocytes. Sotalol significantly increased tau [(128 +/- 7) ms vs. (98 +/- 8) ms, P<0.05] and ADP90 [(405 +/- 13) ms vs. (220 +/- 10) ms, P<0.05] while reduced the tau/APD90 (0.32 +/- 0.05 vs. 0.44 +/- 0.03, P<0.05) compared to control myocytes.</p><p><b>CONCLUSION</b>The differential effect of amiodarone and sotalol on ventricular myocytes tau/APD90 ratio might be responsible for the safety profile of these two drugs.</p>
Asunto(s)
Animales , Conejos , Potenciales de Acción , Amiodarona , Farmacología , Antiarrítmicos , Farmacología , Canales de Calcio Tipo L , Fisiología , Miocitos Cardíacos , Fisiología , Técnicas de Placa-Clamp , Sotalol , FarmacologíaRESUMEN
Nitrobenzene is one of the toxic compounds. Much work had focused on biodegradation of it sofar. Two main pathways for nitrobenzene biodegradation, oxidative and partial reductive pathways, were reviewed in this article. The mechanism of these pathways including involved enzymes and genes was introduce in details. Comparative analysis of the pathways would provide basis for the development and application of biodegradation technology for nitrobenzene and other organic pollutants.