中国病理生理杂志2025，Vol.41Issue(6)：1077-1087,11.DOI:10.3969/j.issn.1000-4718.2025.06.004
健脾化瘀方协同吉西他滨通过Nrf2/SLC7A11/GPX4轴诱导胰腺癌细胞铁死亡并抑制其生长
Jianpi-Huayu decotion combined with gemcitabine induces ferroptosis and inhibits growth of pancreatic cancer cells through Nrf2/SLC7A11/GPX4 axis
摘要
Abstract
AIM:To investigate the effect of Jianpi-Huayu decoction(JPHYD)combined with gemcitabine(GEM)on ferroptosis of pancreatic cancer PANC-1 cells and its mechanism.METHODS:PANC-1 cells were cultured in vitro,and CCK8 method was used to detect the cell viability after different concentrations of JPHYD and GEM,and ap-propriate concentrations were selected for follow-up experiments.EDU assay and clonogenesis assay were used to detect cell proliferation.The apoptosis rate was detected by flow cytometry.Intracellular reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescent probe and lipid peroxidation was detected by BODIPY 581/591C11 staining.The contents of glutathione(GSH),ferrous ion(Fe2+)and malondialdehyde(MDA)in the cells were detected by the kit.The mRNA levels and protein expression levels of Nrf2,HO-1,SLC7A11,GPX4,TFR1 and ACSL4 were detected by RT-qPCR and Western blot.RESULTS:Compared with the control group,the cell viability of PANC-1 treated with JPHYD and GEM was significantly decreased in a concentration-dependent manner.And the combined use of the two can significantly im-prove the cytotoxic effect of GEM and have a synergistic effect;Compared with control group,JPHYD group,GEM group and JPHYD+GEM group can significantly reduce EDU positive efficiency,colony formation numbers and promote cell apoptosis,and the combined group has the most obvious effect.After adding JPHYD+GEM into the cells,the cells be-came rounded and the cell viability decreased.The addition of ferrostatin-1(Fer-1),an inhibitor of ferroptosis,had no significant effect on cell morphology and viability,and the co-treatment with JPHYD+GEM and Fer-1 could reverse the ef-fects of JPHYD+GEM on cell morphology and viability.Compared with control group and GEM group,JPHYD+GEM group can significantly increase the levels of intracellular reactive oxygen species(ROS)and lipid peroxidation,increase the levels of Fe2+and MDA,decrease the levels of GSH,further promote lipid peroxidation and induce ferroptosis.JPHYD+GEM also significantly down-regulated the mRNA and protein expressions of Nrf2,HO-1,SLC7A11 and GPX4,and up-regulated the mRNA and protein expressions of TFR1 and ACSL4.The addition of Fer-1 significantly reversed the activation of iron death in the combined treatment group and reversed its efficacy,and the difference was statistically signif-icant.CONCLUSION:Jianpi Huayu decoction and gemcitabine may induce ferroptosis of PANC-1 cells by inhibiting Nrf2/SLC7A11/GPX4 axis in vitro,thus playing a synergistic anticancer role.关键词
健脾化瘀方/吉西他滨/胰腺癌/铁死亡/Nrf2/SLC7A11/GPX4轴Key words
Jianpi-Huayu decoction/gemcitabine/pancreatic cancer/ferroptosis/Nrf2/SLC7A11/GPX4 axis分类
临床医学引用本文复制引用
陈鑫球,张正则,刘抒伟,朱小玉,赖永恒,方崇锴,黄俊海,赵希琳,钟崇..健脾化瘀方协同吉西他滨通过Nrf2/SLC7A11/GPX4轴诱导胰腺癌细胞铁死亡并抑制其生长[J].中国病理生理杂志,2025,41(6):1077-1087,11.基金项目
国家自然科学基金资助项目(No.82274526) （No.82274526）
广东省自然科学基金资助项目(No.2023A1515011069) （No.2023A1515011069）
广州中医药大学"双一流"与高水平大学学科后备人才培育项目(No.A1-2601-22-415-023) （No.A1-2601-22-415-023）
广州中医药大学第一临床医学院"揭榜挂帅"研究生创新能力提升项目(No.A3-0317-25-110-005) （No.A3-0317-25-110-005）
