南方医科大学学报2024，Vol.44Issue(7)：1425-1430,6.DOI:10.12122/j.issn.1673-4254.2024.07.23
丁酸钠与索拉非尼可能通过YAP诱导铁死亡协同抑制肝癌细胞增殖
Sodium butyrate and sorafenib synergistically inhibit hepatocellular carcinoma cells possibly by inducing ferroptosis through inhibiting YAP
摘要
Abstract
Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.关键词
丁酸钠/索拉非尼/肝癌/铁死亡/YAP/细胞增殖Key words
sodium butyrate/sorafenib/hepatocellular carcinoma/ferroptosis/YAP/proliferation引用本文复制引用
何华星,刘璐琳,刘颖茵,陈纳川,孙素霞..丁酸钠与索拉非尼可能通过YAP诱导铁死亡协同抑制肝癌细胞增殖[J].南方医科大学学报,2024,44(7):1425-1430,6.基金项目
国家自然科学基金(81773429) （81773429）
广东省自然科学基金(2022A1515011631,2024A1515012175) Supported by National Natural Science Foundation of China(81773429). （2022A1515011631,2024A1515012175）
