医药导报2024,Vol.43Issue(3):334-345,12.DOI:10.3870/j.issn.1004-0781.2024.03.002
α-常春藤皂苷通过激活和稳定p53/Noxa信号诱导肝癌细胞凋亡
α-Hederin Induces Apoptosis in Hepato-cellular Carcinoma Cells by Activating and Stabilizing p53/Noxa Signaling Pathway
摘要
Abstract
Objective To investigate the inhibitory effects and mechanisms of α-hederin,an active ingredient in Fruc-tus Akebiae,on hepatocellular carcinoma(HCC)cells.Methods HCC cells were divided into four groups and treated with α-hederin(0,10,20,and 30 μmol·L-1)for 24 h and 48 h,respectively.MTT assays were used to detect the cell proliferation rate,flow cytometry(FCM)was used to detect the apoptotic rate,transcriptomics was used to screen signaling pathways in α-hederin-treated HCC cells,RNA interference was exploited to verify the underlying signaling pathway,and real-time quantitative PCR(qRT-PCR)and Western blotting(WB)were used to detect expression changes of the mRNA and protein of TP53(p53),PMAIP1(Noxa),and apoptosis-associated proteins,Caspase9 and Caspase3.Results α-Hederin induced apoptosis by activa-ting apoptosis-associated proteins,PARP,Caspase9 and Caspase3.Transcriptomics,qRT-PCR,and WB results also showed that α-hederin increased the mRNA and protein expression of p53 and Noxa.Furthermore,α-hederin inhibited the protein degradation of p53 and Noxa,reversing the apoptosis decrease in p53/Noxa siRNA-knocked-down HCC cells.In vivo results showed that α-hederin inhibited the growth of HCC tumors.Conclusion α-hederin may induce the apoptosis of HCC cells by activating and stabilizing the p53/Noxa signaling pathway.关键词
α-常春藤皂苷/肝细胞癌/凋亡/p53/NoxaKey words
α-hederin/Hepatocellular carcinoma/Apoptosis/p53/Noxa分类
医药卫生引用本文复制引用
陈晓静,周莉,刘凯琪,段菊凤,刘明,李洪亮,汪选斌..α-常春藤皂苷通过激活和稳定p53/Noxa信号诱导肝癌细胞凋亡[J].医药导报,2024,43(3):334-345,12.基金项目
国家自然科学基金面上项目(82274155) (82274155)
湖北省科技厅对外合作项目(2022EHB046) (2022EHB046)
湖北省科技厅自然基金面上项目(2023AFB925) (2023AFB925)
武当特色中药研究湖北省重点实验室开放课题(WDCM2018002,WDCM201917,WDCM201918) (WDCM2018002,WDCM201917,WDCM201918)
"十四五"湖北省高等学校优势特色学科群(现代医学)项目(2022XKQY3). (现代医学)