RESUMEN
This study examined the molecular mechanisms of apicidin in the modulation of human ovarian cancer SKOV-3 cells invasion and migration. Apicidin markedly decreased histone deacetylase 4 (HDAC4) expression and blocked cell migration and invasion. Cell migration was inhibited via down-regulation of matrix metalloproteinase-2 (MMP-2) and up-regulation of RECK in the HDAC4-blocked SKOV-3 cells. Apicidin significantly suppressed the binding of HDAC4 to Sp1 binding elements of the RECK promoter via repression of HDAC4. In an in vivo model, apicidin suppressed the growth of transplanted SKOV-3 cells by down-regulating HDAC4 and MMP-2. Apicidin may potentially be used as an anti-cancer agent for inhibition of cancer cell migration and invasion through the repression of MMP-2 which is related to the reduction of HDAC4.
Asunto(s)
Adenocarcinoma/patología , Inhibidores de Histona Desacetilasas/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias Ováricas/patología , Péptidos Cíclicos/farmacología , Proteínas Represoras/antagonistas & inhibidores , Animales , Línea Celular Tumoral/efectos de los fármacos , Línea Celular Tumoral/metabolismo , Línea Celular Tumoral/trasplante , Movimiento Celular/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Proteínas Ligadas a GPI/biosíntesis , Proteínas Ligadas a GPI/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Histona Desacetilasas , Humanos , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 2 de la Matriz/genética , Inhibidores de la Metaloproteinasa de la Matriz , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Regiones Promotoras Genéticas , Unión Proteica/efectos de los fármacos , Proteolisis , ARN Interferente Pequeño/farmacologíaRESUMEN
Biliary duct injuries are frequently iatrogenic, being associated with surgery for gallbladder stones. However, blunt abdominal trauma such as a motor vehicle crash is a rare cause of extrahepatic biliary stricture. A few reports have been published on biliary strictures treated with endoscopic therapy. In the present study, we describe a suprapancreatic biliary stricture associated with mesenteric tear following road traffic accident. We performed endoscopic stent placement, which was successful in relieving the biliary stricture.