目的:探讨岩藻多糖对胰腺癌的影响,并分析其机制。方法:MTT法分析细胞增殖抑制率,GEPIA数据库分析G3BP1在胰腺癌组织中的表达水平及与生存率的关系。qRT-PCR分析GTP酶激活蛋白结合蛋白1(Ras-GTPase-activating protein binding proteins...目的:探讨岩藻多糖对胰腺癌的影响,并分析其机制。方法:MTT法分析细胞增殖抑制率,GEPIA数据库分析G3BP1在胰腺癌组织中的表达水平及与生存率的关系。qRT-PCR分析GTP酶激活蛋白结合蛋白1(Ras-GTPase-activating protein binding proteins,G3BP1)水平,Western blot法分析p-NF-κBp65、NF-κBp65和IκB-α水平。免疫共沉淀检测G3BP1与p-NF-κBp65之间相互作用。敲低或G3BP1过表达,观察其对岩藻多糖调控细胞增殖以及NF-κB信号通路的影响。裸鼠成瘤实验验证岩藻多糖对裸鼠体内瘤体的瘤重、瘤体积及G3BP1、p-NF-κBp65、NF-κBp65和IκBα水平的影响。结果:1~32μg/mL岩藻多糖抑制capan-1细胞增殖,岩藻多糖48 h IC_(50)为7.729μg/mL。G3BP1在胰腺癌肿瘤组织中的表达明显高于正常组织,G3BP1高表达患者的生存率低于G3BP1低表达患者。2、4、8μg/mL岩藻多糖能下调G3BP1、p-NF-κBp65,上调IκBα水平。Co-IP实验发现G3BP1与p-NF-κBp65相互结合,并且岩藻多糖作用后结合能力降低。敲低G3BP1能促进岩藻多糖抑制capan-1细胞增殖,下调G3BP1、p-NF-κBp65,上调IκBα水平(P<0.05);G3BP过表达能下调岩藻多糖抑制capan-1细胞增殖效果,上调G3BP1、p-NF-κBp65,下调IκBα水平(P<0.05)。体内实验显示,敲低G3BP1能促进岩藻多糖减少瘤体体积、瘤体质量,下调瘤体G3BP1、p-NF-κBp65,上调IκBα水平(P<0.05)。结论:岩藻多糖抑制capan-1细胞增殖,对体内移植瘤抑瘤效果显著,其机制与调控G3BP1/NF-κB信号通路有关。展开更多
BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver ...BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.展开更多
文摘目的:探讨岩藻多糖对胰腺癌的影响,并分析其机制。方法:MTT法分析细胞增殖抑制率,GEPIA数据库分析G3BP1在胰腺癌组织中的表达水平及与生存率的关系。qRT-PCR分析GTP酶激活蛋白结合蛋白1(Ras-GTPase-activating protein binding proteins,G3BP1)水平,Western blot法分析p-NF-κBp65、NF-κBp65和IκB-α水平。免疫共沉淀检测G3BP1与p-NF-κBp65之间相互作用。敲低或G3BP1过表达,观察其对岩藻多糖调控细胞增殖以及NF-κB信号通路的影响。裸鼠成瘤实验验证岩藻多糖对裸鼠体内瘤体的瘤重、瘤体积及G3BP1、p-NF-κBp65、NF-κBp65和IκBα水平的影响。结果:1~32μg/mL岩藻多糖抑制capan-1细胞增殖,岩藻多糖48 h IC_(50)为7.729μg/mL。G3BP1在胰腺癌肿瘤组织中的表达明显高于正常组织,G3BP1高表达患者的生存率低于G3BP1低表达患者。2、4、8μg/mL岩藻多糖能下调G3BP1、p-NF-κBp65,上调IκBα水平。Co-IP实验发现G3BP1与p-NF-κBp65相互结合,并且岩藻多糖作用后结合能力降低。敲低G3BP1能促进岩藻多糖抑制capan-1细胞增殖,下调G3BP1、p-NF-κBp65,上调IκBα水平(P<0.05);G3BP过表达能下调岩藻多糖抑制capan-1细胞增殖效果,上调G3BP1、p-NF-κBp65,下调IκBα水平(P<0.05)。体内实验显示,敲低G3BP1能促进岩藻多糖减少瘤体体积、瘤体质量,下调瘤体G3BP1、p-NF-κBp65,上调IκBα水平(P<0.05)。结论:岩藻多糖抑制capan-1细胞增殖,对体内移植瘤抑瘤效果显著,其机制与调控G3BP1/NF-κB信号通路有关。
文摘BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.
