Magnesium cantharidate suppresses PP2A and ERK1/2 pathway to inhibit hepatocellular carcinoma cells

查看全文 作　　者：Ze [1]Wang;Yu-Xi [2]Huang;Tian-Mu [2]He;Xiang-Yu [2]Tan;Xiao-Fei [2,3]Li;Yun [2,3]Liu;Rong [2,3]Yan 机构地区：[1]School of Pharmacy,Zunyi Medical University,Zunyi 563000,China;[2]School of Basic Medicine,Zunyi Medical University,Zunyi 563000,China;[3]Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines,Zunyi Medical University,Zunyi 563000,China 出　　处：《Toxicology Advances》索引2024年第6卷第1期,共12页 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). 摘　　要：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. 关 键 词：magnesium cantharidate ERK1/2 HCC PP2A