Currently, chemoresistance seriously attenuates the curative outcome of liver cancer. The purpose of our work was to investigate the influence of 6-shogaol on the inhibition of 5-fluorouracil (5-FU) in liver cancer. T...Currently, chemoresistance seriously attenuates the curative outcome of liver cancer. The purpose of our work was to investigate the influence of 6-shogaol on the inhibition of 5-fluorouracil (5-FU) in liver cancer. The cell viability of cancer cells was determined by MTT assay. Liver cancer cell apoptosis and the cell cycle were examined utilizing flow cytometry. Moreover, qRT–PCR and western blotting was used to analyse the mRNA and protein expression levels, respectively. Immunohistochemistry assays were used to examine multidrug resistance protein 1 (MRP1) expression in tumour tissues. In liver cancer cells, we found that 6-shogaol-5-FU combination treatment inhibited cell viability, facilitated G0/G1 cell cycle arrest, and accelerated apoptosis compared with 6-shogaol or 5-FU treatment alone. In cancer cells cotreated with 6-shogaol and 5-FU, AKT/mTOR pathway- and cell cycle-related protein expression levels were inhibited, and MRP1 expression was downregulated. AKT activation or MRP1 increase reversed the influence of combination treatment on liver cancer cell viability, apoptosis and cell cycle arrest. The inhibition of AKT activation to the anticancer effect of 6-shogaol-5-FU could be reversed by MRP1 silencing. Moreover, our results showed that 6-shogaol-5-FU combination treatment notably inhibited tumour growth in vivo. In summary, our data demonstrated that 6-shogaol contributed to the curative outcome of 5-FU in liver cancer by inhibiting the AKT/mTOR/MRP1 signalling pathway.展开更多
目的:通过对6-姜烯酚(6-SH)与NF-κB分子间的作用方式,评价6-SH对NF-κB信号通路的影响。方法:利用蛋白质组学方法及分子对接技术,使用western-blotting和Discoveray Studio 2.5分子建模和模拟环境软件,采用模拟蒙特卡罗方法在Ligand Fi...目的:通过对6-姜烯酚(6-SH)与NF-κB分子间的作用方式,评价6-SH对NF-κB信号通路的影响。方法:利用蛋白质组学方法及分子对接技术,使用western-blotting和Discoveray Studio 2.5分子建模和模拟环境软件,采用模拟蒙特卡罗方法在Ligand Fit模块中将6-姜烯酚与NF-κB分子的活性位点进行柔性对接,观察配体结合取向、结合构象以及形状匹配等多种表现。结果:6-SH能够抑制NF-κB蛋白的表达;6-SH与NF-κB的Tyr57,Val58,Cys59,Tyr143,Lys145,Lys146氨基酸残基末端结合,并且与Lys145之间产生交互作用,最终一致性分析得分为41.27,配体内部的能量为-3.52。结论:6-SH通过与NF-κB活性位点结合,影响其调控的信号转导通路。展开更多
文摘Currently, chemoresistance seriously attenuates the curative outcome of liver cancer. The purpose of our work was to investigate the influence of 6-shogaol on the inhibition of 5-fluorouracil (5-FU) in liver cancer. The cell viability of cancer cells was determined by MTT assay. Liver cancer cell apoptosis and the cell cycle were examined utilizing flow cytometry. Moreover, qRT–PCR and western blotting was used to analyse the mRNA and protein expression levels, respectively. Immunohistochemistry assays were used to examine multidrug resistance protein 1 (MRP1) expression in tumour tissues. In liver cancer cells, we found that 6-shogaol-5-FU combination treatment inhibited cell viability, facilitated G0/G1 cell cycle arrest, and accelerated apoptosis compared with 6-shogaol or 5-FU treatment alone. In cancer cells cotreated with 6-shogaol and 5-FU, AKT/mTOR pathway- and cell cycle-related protein expression levels were inhibited, and MRP1 expression was downregulated. AKT activation or MRP1 increase reversed the influence of combination treatment on liver cancer cell viability, apoptosis and cell cycle arrest. The inhibition of AKT activation to the anticancer effect of 6-shogaol-5-FU could be reversed by MRP1 silencing. Moreover, our results showed that 6-shogaol-5-FU combination treatment notably inhibited tumour growth in vivo. In summary, our data demonstrated that 6-shogaol contributed to the curative outcome of 5-FU in liver cancer by inhibiting the AKT/mTOR/MRP1 signalling pathway.
文摘目的:通过对6-姜烯酚(6-SH)与NF-κB分子间的作用方式,评价6-SH对NF-κB信号通路的影响。方法:利用蛋白质组学方法及分子对接技术,使用western-blotting和Discoveray Studio 2.5分子建模和模拟环境软件,采用模拟蒙特卡罗方法在Ligand Fit模块中将6-姜烯酚与NF-κB分子的活性位点进行柔性对接,观察配体结合取向、结合构象以及形状匹配等多种表现。结果:6-SH能够抑制NF-κB蛋白的表达;6-SH与NF-κB的Tyr57,Val58,Cys59,Tyr143,Lys145,Lys146氨基酸残基末端结合,并且与Lys145之间产生交互作用,最终一致性分析得分为41.27,配体内部的能量为-3.52。结论:6-SH通过与NF-κB活性位点结合,影响其调控的信号转导通路。
