RESUMO
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.
Assuntos
Adenocarcinoma/patologia , Inibidores de Histona Desacetilases/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias Ovarianas/patologia , Peptídeos Cíclicos/farmacologia , Proteínas Repressoras/antagonistas & inibidores , Animais , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Linhagem Celular Tumoral/transplante , Movimento Celular/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Feminino , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histona Desacetilases , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/genética , Inibidores de Metaloproteinases de Matriz , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Regiões Promotoras Genéticas , Ligação Proteica/efeitos dos fármacos , Proteólise , RNA Interferente Pequeno/farmacologiaRESUMO
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.