RESUMEN
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.
Asunto(s)
Apoptosis/efectos de los fármacos , Planta del Astrágalo/química , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Polisacáridos/farmacología , Receptor Notch1/metabolismo , Apoptosis/genética , Carcinoma Hepatocelular/genética , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Hepáticas/genética , Metástasis de la Neoplasia , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVE: To optimize the preparation process of Erigeron breviscapus sustained-release pellets. METHODS: A mathematical model of relationship between the independent variables and dependent variable of the preparation process of Erigeron breviscapus sustained-release pellets was established by using back-propagation (BP) artificial neural networks (ANN), and the preparation process parameters were optimized with particle swarm optimization (PSO) algorithm. RESULTS: The pellets prepared according to the optimized preparation process parameters had significant effect of sustained-releasing. Drug release from the pellets was controlled by both diffusion and matrix corrosion. CONCLUSION: Combining BP ANN modeling with PSO algorithm provides an effective way to solve the multi-dimensional optimization problem of complicated nonlinear systems in pharmaceutical technology.