昆明医科大学学报2026，Vol.47Issue(8)：38-47,10.DOI:10.12259/j.issn.2095-610X.S20260804
基于Keap1/Nrf2/HO-1信号通路探讨毛兰素对前列腺癌细胞铁死亡的影响
Effects of Erianin on Ferroptosis in Prostate Cancer Cells via the Keap1/Nrf2/HO-1 Signaling Pathway
摘要
Abstract
Objectives To investigate whether erianin induces ferroptosis in prostate cancer cells by regula-ting the Keap1/Nrf2/HO-1 signaling pathway.Methods Human prostate cancer cell lines DU145 and PC-3 were cultured.Cell viability was detected by CCK-8 assay,cell proliferation by colony formation assay,cell invasion by Transwell assay,and cell apoptosis by flow cytometry.Intracellular reactive oxygen species(ROS)content was analyzed using the ROS-specific probe DCFH-DA,and the levels of malondialdehyde(MDA)and glutathione(GSH)were determined.Western blot was used to detect the expression of metastatic phenotypic markers(vimentin,N-cadherin,slug,snail,andMMP-9),ferroptosis-negative regulatory proteins(GPX4,CHAC2,SLC40A1,SLC7A11,and glutaminase),and proteins related to the Keap1/Nrf2/HO-1 signaling pathway.Results Compared with the control group,erianin significantly reduced the viability of prostate cancer cells(DU 145,PC-3)and inhibited their proliferation,migration,and invasion abilities(P＜0.05).Erianin inhibited the migration of prostate cancer cells by downregulating the mesenchymal markers(vimentin,N-cadherin,slug,snail,and MMP-9)and upregulating the epithelial marker E-cadherin.ROS accumulation,GSH depletion,and lipid peroxidation were significantly increased(P＜0.05).Erianin-induced prostate cancer cell death could be rescued by co-treatment with the ROS inhibitor N-acetyl-L-cysteine(NAC)and glutathione(GSH).After erianin treatment,the proportion of Phen Green SK-positive cells(detecting intracellular free Fe2+)was significantly decreased(P＜0.05).Transmission electron microscopy(TEM)revealed mitochondrial matrix condensation and cristae enlargement in erianin-treated prostate cancer cells.Additionally,erianin treatment significantly downregulated the expression of ferroptosis-negative regulatory proteins(GPX4,CHAC2,SLC40A1,SLC7A11,and glutaminase)(P＜0.05).Co-treatment with ferroptosis inhibitors(Liproxstatin-1,Lip-1;or Ferrostatin-1,Fer-1)blocked erianin-induced prostate cancer cell death.Erianin increased Keap1 protein expression while decreasing the expression of Nrf2,HO-1,and NQO1 proteins in cells(P＜0.05).CPUY192018 enhanced ferroptosis in prostate cancer cells,indicating that erianin induces ferroptosis through targeting the Keap1/Nrf2/HO-1 signaling pathway.Conclusion Erianin induces cell death and suppresses prostate cancer cell migration by targeting the Keap1/Nrf2/HO-1 signaling pathway.关键词
毛兰素/Keap1/Nrf2/HO-1/前列腺癌/铁死亡Key words
Erianin/Keap1/Nrf2/HO-1 Signaling pathway/Prostate cancer/Ferroptosis分类
医药卫生引用本文复制引用
赵海英,刘建荣,向阳..基于Keap1/Nrf2/HO-1信号通路探讨毛兰素对前列腺癌细胞铁死亡的影响[J].昆明医科大学学报,2026,47(8):38-47,10.基金项目
黑龙江省卫生健康委员会科研基金(H186150198) （H186150198）
