RESUMO
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death worldwide. Astragalus polysaccharide (APS), the primary active component extracted from a traditional Chinese medicinal herb Astragalus membranaceus, has been proved to exert a marked inhibitory effect on a number of types of human solid tumors. In the present study, we aimed to examine the effects of APS on the survival of the HCC cell line H22 and to elucidate the underlying regulatory mechanisms responsible for these effects. Our results revealed that the mRNA and protein expression of Notch1 was significantly upregulated in the HCC tissues compared with that in the normal tissues. APS decreased cell viability and induced the apoptosis of HCC cells in a concentration-dependent manner, which were evaluated using a cell counting kit-8 (CCK-8) assay and flow cytometric analysis, respectively. Furthermore, APS regulated the expression of apoptosis-related genes (Bcl-2 and BAX) and proteases (caspase-3 and -8). Mechanically, Notch1 expression was found to be suppressed in HCC cells, and further analysis indicated that Notch1 knockdown by siRNA significantly reduced cell viability, suppressed the metastatic capacity and enhanced the apoptosis of HCC cells. Taken together, these findings suggest that Notch1 may be a potential therapeutic target for the treatment of HCC.
Assuntos
Apoptose/efeitos dos fármacos , Astrágalo/química , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Polissacarídeos/farmacologia , Receptor Notch1/metabolismo , Apoptose/genética , Carcinoma Hepatocelular/genética , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/genética , Metástase Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
RATIONALE AND OBJECTIVES: To evaluate multidetector computed tomography (MDCT) for detecting the early changes and dynamic evolution of acute mesenteric ischemia (AMI) induced by the ligation of superior mesenteric vein (SMV) in an experimental porcine model. MATERIALS AND METHODS: Twelve pigs were randomly assigned to three experimental groups, and one control group with three pigs in each group. After laparotomy, the SMV was separated and ligated in nine pigs and separated without ligation in three controls. MDCT pre- and postcontrast with arterial, venous, and delayed phase scans, and CT angiography reconstructions of mesenteric vessels were carried out at preoperation, 6 hours, 12 hours, and 18 hours after ligation. The findings of mesenteric vessels, bowel, abdominal cavity at pre- and postoperation, and dynamic evolution were correlated with pathology. RESULTS: AMI-induced pathological changes were identified in all nine experimental pigs. MDCT angiography clearly delineated main trunk of the SMV, peripheral major and minor tributaries up to brushy vasa recta, and the location and shape of ligations. The early ischemic findings were bowel wall thickening, mesenteric edema, ascites, and pronounced bowel enhancement. Superior mesenteric artery and its major branches appeared spasm with poor filling and delayed and prolonged visualization. SMV and its tributaries were poorly delineated with delayed opacification. We also saw thinning of bowel wall, dilatating bowel with fluid, aggravating mesenteric edema and ascites, and poor enhanced bowel over time. CONCLUSION: MDCT detects early changes of mesenteric ischemia and its evolution after ligation of porcine SMV, and may find application in early diagnosis of human venous occlusive AMI.
