Background:Magnesium cantharidate(MC)is a protein phosphatase 2A(PP2A)inhibitor antitumor drug.However,its antitumor mechanism in hepatocellular carcinoma cell(HCC)remains unclear.Methods:PP2A lentiviral vector over e...Background:Magnesium cantharidate(MC)is a protein phosphatase 2A(PP2A)inhibitor antitumor drug.However,its antitumor mechanism in hepatocellular carcinoma cell(HCC)remains unclear.Methods:PP2A lentiviral vector over expression strategy was utilized both in vivo and in vitro to explore the antitumor effect in MC and okadaic acid(OA).Tumor weight was detected in mice after MC and OA exposure.Cell proliferation,cell cycle,apoptosis rate,and western blotting were detected to explore the effects on MC and OA in human hepatocarcinoma SMMC-7721 cells.Results:In vivo results demonstrated that MC inhibited HCC progression while OA promoted tumor growth.In vitro results demonstrated that MC effectively inhibited the growth of SMMC-7721 cells by arresting the cell cycle at the G2/M phase with inhibiting Cdc25C and activating the phosphorylation of the Cdc2 protein.Flow cytometry results further showed that MC increased apoptosis.Furthermore,the expression of phosphorylated ERK1/2 was lower in the MC group but higher in the OA group.Molecular docking results showed that MC docked well with ERK1/2.Conclusions:MC inhibited HCC progression by suppressing the growth and activating the apoptosis of cancer cells and suppressing the expression of PP2A and ERK1/2.展开更多
PP2C(PP2C-type protein phosphatases)蛋白磷酸酶是一类丝氨酸/苏氨酸残基蛋白磷酸酶,植物体内目前已经发现了4种PP2C蛋白磷酸酶:ABI,AtP2C-HAB1,AtPP2CA以及MP2C。大量的研究表明植物PP2C蛋白磷酸酶参与了ABA信号转导途径的负调控功...PP2C(PP2C-type protein phosphatases)蛋白磷酸酶是一类丝氨酸/苏氨酸残基蛋白磷酸酶,植物体内目前已经发现了4种PP2C蛋白磷酸酶:ABI,AtP2C-HAB1,AtPP2CA以及MP2C。大量的研究表明植物PP2C蛋白磷酸酶参与了ABA信号转导途径的负调控功能。就高等植物PP2C的分类及其对ABA信号转导途径的负调控功能的研究进展进行了综述。展开更多
文摘蛋白磷酸酶2C(protein phosphatase 2C,PP2Cs)家族是植物细胞去除磷酸化蛋白中磷酸基团的重要蛋白磷酸酶。拟南芥含有80多个编码PP2Cs的基因,然而大部分成员在植物抗逆反应中的功能仍有待研究。本文发现拟南芥PP2C31(At2g40860)基因的表达受高盐抑制,其T-DNA插入突变体(pp2c31-1突变体和pp2c31-2突变体)表现出对高盐胁迫的耐受性且Na+含量较低。实时定量PCR(quantitative real time-PCR,qRT-PCR)分析发现,PP2C31基因在植物体各组织均有表达;亚细胞定位结果显示PP2C31蛋白定位于细胞质和细胞核中。利用脱落酸合成抑制剂和外源脱落酸处理发现,突变体植株的高盐耐受性和PP2C31基因的表达均不受脱落酸的影响。研究结果表明:PP2C31蛋白是拟南芥响应高盐胁迫的一个非脱落酸依赖的负调控组分。
基金The research was financially supported by the National Natural Science Foundation of China(no.81760746)Science and Technology Department of Zunyi city of Guizhou province of China([2020]7)Guizhou Provincial Science&Technology Program(ZK[2022]615).
文摘Background:Magnesium cantharidate(MC)is a protein phosphatase 2A(PP2A)inhibitor antitumor drug.However,its antitumor mechanism in hepatocellular carcinoma cell(HCC)remains unclear.Methods:PP2A lentiviral vector over expression strategy was utilized both in vivo and in vitro to explore the antitumor effect in MC and okadaic acid(OA).Tumor weight was detected in mice after MC and OA exposure.Cell proliferation,cell cycle,apoptosis rate,and western blotting were detected to explore the effects on MC and OA in human hepatocarcinoma SMMC-7721 cells.Results:In vivo results demonstrated that MC inhibited HCC progression while OA promoted tumor growth.In vitro results demonstrated that MC effectively inhibited the growth of SMMC-7721 cells by arresting the cell cycle at the G2/M phase with inhibiting Cdc25C and activating the phosphorylation of the Cdc2 protein.Flow cytometry results further showed that MC increased apoptosis.Furthermore,the expression of phosphorylated ERK1/2 was lower in the MC group but higher in the OA group.Molecular docking results showed that MC docked well with ERK1/2.Conclusions:MC inhibited HCC progression by suppressing the growth and activating the apoptosis of cancer cells and suppressing the expression of PP2A and ERK1/2.
文摘PP2C(PP2C-type protein phosphatases)蛋白磷酸酶是一类丝氨酸/苏氨酸残基蛋白磷酸酶,植物体内目前已经发现了4种PP2C蛋白磷酸酶:ABI,AtP2C-HAB1,AtPP2CA以及MP2C。大量的研究表明植物PP2C蛋白磷酸酶参与了ABA信号转导途径的负调控功能。就高等植物PP2C的分类及其对ABA信号转导途径的负调控功能的研究进展进行了综述。
