江苏大学学报(医学版)2025,Vol.35Issue(4):311-317,7.DOI:10.13312/j.issn.1671-7783.y240024
3,3'-二吲哚甲烷通过诱导铁死亡抑制紫杉醇耐药非小细胞肺癌A549/T细胞增殖
3,3'-Diindolylmethane inhibits the proliferation of paclitaxel-resistant non-small cell lung cancer A549/T cells by inducing ferroptosis
摘要
Abstract
Objective:To investigate the effect of 3,3'-diindolylmethane(DIM)on paclitaxel-resistant non-small cell lung cancer A549/T cells and explore its underlying mechanism.Methods:Western blotting was used to detect transferrin receptor(TFRC),solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in human normal bronchial epithelial BEAS-2b cells,human NSCLC A549 cells,paclitaxel-resistant human NSCLC A549/T cells,and human large cell lung cancer H460 cells to select the optimal cell line.A549 and A549/T cells were treated with various concentrations of DIM(0,20,40,80,160 μmol/L),and cell proliferation was assessed by CCK-8 assay;and the expression of TFRC,SLC7A11 and GPX4 proteins in A549/T cells were determined by Western blotting to screen out the optimal DIM concentration.Additionally,A549/T cells were divided into the control group,which was cultured in high-glucose medium containing 10%fetal bovine serum for 24 h;the Erastin group,treated with 10 μmol/L Erastin for 12 h alone;the DIM group,treated only with 80 μmol/L DIM for 24 h;the DIM+Erastin group,cells were pre-treated with 10 μmol/L Erastin for 12 h,then treated with 80 μmol/L DIM in the following 24 h.Cell viability was detected by CCK-8 assay,and the expression of TFRC,SLC7A11 and GPX4 proteins was assessed by Western blotting.Results:Compared with the BEAS-2b group,TFRC and SLC7A11 expression was significantly increased in A549 cells(P<0.05),TFRC,SLC7A11 and GPX4 expression was significantly increased in A549/T cells(P<0.05).No significant differences in TFRC,SLC7A11 and GPX4 expression were observed in H460 cells(P>0.05).In A549/T cells,compared with the 0 μmol/L group,the expression of TFRC,SLC7A11 and GPX4 proteins showed significant alterations in the 80 μmol/L DIM group(all P<0.05).Compared with 0 μmol/L DIM group,in A549 cells,cell viability was significantly decreased in 20,40,80 and 160 μmol/L DIM groups(all P<0.05);in A549/T cells,cell proliferation was significantly decreased in 80 and 160 μmol/L DIM groups(all P<0.05).In A549/T cells,compared with the control group,DIM group,Erastin group and DIM+Erastin group showed a significant increase in TFRC expression(all P<0.05),while the expression of SLC7A11 and GPX4 proteins significantly decreased(all P<0.05),and cell proliferation significantly decreased(all P<0.05).Conclusion:DIM may inhibit the proliferation of paclitaxel-resistant non-small cell lung cancer A549/T cells by inducing ferroptosis,and ferroptosis inducers could be used to enhance the anti-cancer effect of DIM.关键词
3,3'-二吲哚甲烷/紫杉醇耐药非小细胞肺癌/非小细胞肺癌/铁死亡/肿瘤耐药/A549/T细胞Key words
3,3'-diindolylmethane/paclitaxel-resistant non-small cell lung cancer/non-small cell lung cancer/ferroptosis/tumor resistance/A549/T cells分类
医药卫生引用本文复制引用
刘婷婷,徐伟,叶洋,陆荣柱,姜袁越,高乾乾..3,3'-二吲哚甲烷通过诱导铁死亡抑制紫杉醇耐药非小细胞肺癌A549/T细胞增殖[J].江苏大学学报(医学版),2025,35(4):311-317,7.基金项目
昆山市市级科技专项(KSZ2153) (KSZ2153)
江苏大学医教协同创新基金一般项目(YDYY2023052) (YDYY2023052)