RESUMEN
Overexpression of ECHS1 occurs in different cancers, including hepatocellular carcinoma (HCC). ECHS1 is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of ECHS1 knockdown on the regulation of HCC growth. ECHS1 shRNA suppressed the expression of ECHS1 protein in HepG2 cells compared to the negative control vector-transfected HCC cells. ECHS1 knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. Akt activation and the expression of various cell cycle-related genes were inhibited following ECHS1 knockdown. ECHS1 shRNA suppressed hepatocellular carcinoma growth in tumor xenograft mice. These data demonstrate that ECHS1 may play a role in HCC progression, suggesting that inhibition of ECHS1 expression using ECHS1 shRNA should be further evaluated as a novel target for the control of HCC.
Asunto(s)
Proliferación Celular , Enoil-CoA Hidratasa/genética , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Animales , Apoptosis , Carcinoma Hepatocelular/genética , Movimiento Celular , Supervivencia Celular , Células Cultivadas , Cisplatino , Enoil-CoA Hidratasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Hep G2 , Humanos , Etiquetado Corte-Fin in Situ , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismoRESUMEN
OBJECTIVE: To investigate the protective effect of lycium barbarum polysaccharides (LBP) against heat stress-induced apoptosis of germ cells in rats and its action mechanism. METHODS: Ninety male Sprague-Dawley rats were randomly divided into five groups of 18 each: control, heat stress (HS), high-dose LBP, median-dose LBP and low-dose LBP. The rats of the three LBP groups were given LBP by intragastric administration at 100 mg/(kg x d), 50 mg/(kg x d) and 10 mg/(kg x d) respectively for 14 days, and on the 15th day they, together with those of the HS group, were exposed to a heat of 43 degrees C for 30 minutes. At 24 h, 48 h and 7 d after heat stress, the animals were killed by cervical dislocation, followed by observation of the apoptotic germ cells by TUNEL, determination of the expression of Caspase-3 by immunohistochemistry and detection of cytochrome C in the cytosol by ELISA. RESULTS: Compared with the HS group, the three LBP groups showed statistically significant decreases in the apoptosis index (P<0.05), the expression level of Caspase-3 in germ cells (P<0.05) and the concentration of cytochrome C in the cytosol (P<0.05). CONCLUSION: LBP can inhibit cytochrome C release from mitochondria, decrease the expression of Caspase-3 and hence reduce the apoptosis of germ cells. It thus can be deduced that LBP can protect germ cells against apoptosis via the mitochondrial pathway.