中国肿瘤生物治疗杂志2025，Vol.32Issue(3)：294-300,7.DOI:10.3872/j.issn.1007-385x.2025.03.009
积雪草苷通过cAMP/PKA/CREB信号通路抑制肝细胞癌Huh7细胞的恶性生物学行为
Asiaticoside inhibits the malignant biological behavior of hepatocellular carcinoma Huh7 cells via the cAMP/PKA/CREB signaling pathway
摘要
Abstract
Objective:To investigate whether asiaticoside(ASI)regulates the malignant biological behavior of hepatocellular carcinoma Huh7 cells via the cyclic adenosine monophosphate/protein kinase A/cAMP-response element binding protein(cAMP/PKA/CREB)signaling pathway.Methods:After determining the suitable ASI concentration and treatment duration using MTT assay,Huh7 cells were divided into the following groups:control,ASI-L(20 μmol/L),ASI-M(40 μmol/L),ASI-H(80 μmol/L),and ASI-H+Forskolin(80 μmol/L ASI+100 μmol/L cAMP activator Forskolin)groups.After 48 h of treatment,cell proliferation was assessed using MTT and colony formation assays;cell migration and invasion were analyzed using Transwell assays;apoptosis was detected using an Annexin V-FITC apoptosis detection kit.The secretion level of cAMP and the protein expression levels of phosphorylated PKA(p-PKA)and phosphorylated CREB(p-CREB)were evaluated using ELISA and Western blotting,respectively.A subcutaneous xenograft model was established by injecting Huh7 cells into the right abdomen of nude mice.ASI was administered by gavage at doses of 5,15,and 45 mg/kg for 4 weeks.Tumors were then harvested and weighed.Results:Treatment with 40 μmol/L ASI for 48 hours(close to the IC₅₀)was determined to be the appropriate concentration and duration.Compared with the control group,the ASI-L,ASI-M,and ASI-H groups showed significantly reduced Huh 7 cell proliferation,colony formation,migration,invasion,cAMP levels,and expression of p-PKA/PKA and p-CREB/CREB(all P<0.05),while apoptosis rates were significantly increased(P<0.05).Compared with the ASI-H group,the ASI-H+Forskolin group exhibited significantly increased proliferation,colony formation,migration,invasion,cAMP level,and expression of p-PKA/PKA and p-CREB/CREB(all P<0.05),but apoptosis was significantly reduced(all P<0.05).In the nude mouse xenograft model,ASI at 5,15,and 45 mg/kg markedly decreased tumor weight in nude mice(all P<0.05).Conclusion:ASI inhibits the malignant biological behaviors and promotes apoptosis of Huh7 cells,as well as suppresses tumor growth in nude mice,by downregulating the expression of proteins in the cAMP/PKA/CREB signaling pathway.关键词
积雪草苷/肝细胞癌/Huh7细胞/cAMP/PKA/CREB信号通路Key words
asiaticoside/hepatocellular carcinoma/Huh7 cell/cAMP/PKA/CREB signaling pathway分类
医药卫生引用本文复制引用
刘志超,党同科,满高亚,陈鹏..积雪草苷通过cAMP/PKA/CREB信号通路抑制肝细胞癌Huh7细胞的恶性生物学行为[J].中国肿瘤生物治疗杂志,2025,32(3):294-300,7.基金项目
济宁医学院教师科研扶持项目(No.JYFC2019FKJ301) （No.JYFC2019FKJ301）
