RESUMO
Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/ß-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/ß-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Fatores de Transcrição SOXC/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Endométrio/patologia , Feminino , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Propofol/administração & dosagem , Ensaio Tumoral de Célula-Tronco , Proteínas Wnt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismoRESUMO
Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.
Assuntos
Animais , Feminino , Apoptose/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Fatores de Transcrição SOXC/metabolismo , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Endométrio/patologia , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Propofol/administração & dosagem , Ensaio Tumoral de Célula-Tronco , Proteínas Wnt/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Abstract Radio frequency heating (RFH) provides higher efficiency and more uniform heating zone compared with conventional method. The aim of present work is to evaluate the effect of RFH (at 90 °C for 5 or 10 min) on the changes in composition (protein oxidation and fat distribution), microstructure, flow characteristic and rehydration property of infant milk powder. The results indicate that the concentration of protein dityrosine was slightly enhanced, more free fat appeared on powder surfaces (> 50% increase), and porosity in powder matrix as tested by SEM was increased after RFH treatment. For powder flowability, raw sample had low cohesiveness (specific energy = 4.39 mJ/g), and RFH provided better flowability and decreased compressibility. Moreover, RFH had some negative impacts on wettability and solubility of powder particles with contact angle increase at least 5% and solubility decrease of 2%~4%, indicating worse rehydration abilities. Guggenheim-Anderson-de Boer (GAB) model was applied to fit moisture vapor sorption isotherms, and longer RFH duration leading to higher c values (about 63% increase at 10 min). In addition, the RFH initiated browning reaction as CIE a* values increased from -1.8 to -1.3.