南方医科大学学报2025，Vol.45Issue(12)：2551-2560,10.DOI:10.12122/j.issn.1673-4254.2025.12.03
丝氨酸蛋白酶抑制剂E1过表达通过诱导M2型巨噬细胞极化促进三阴性乳腺癌细胞增殖与紫杉醇耐药
SERPINE1 overexpression promotes proliferation and paclitaxel resistance of triple-negative breast cancer cells by inducing M2 macrophage polarization
摘要
Abstract
Objective To investigate the regulatory effect of Serpin Family E Member 1(SERPINE1)on immune microenvironment and paclitaxel(PTX)resistance of triple-negative breast cancer(TNBC)cells.Methods CCK-8 assay was used to determine the half-maximal inhibitory concentration of PTX in TNBC cell line MDA-MB-231.In wild-type MDA-MB-231 cells and a PTX-resistant MDA-MB-231 cell line(MDA-MB-231/PTX)established by stepwise increasing low-dose PTX treatment,the effects of Western blot-verified transfection with SERPINE1 overexpression plasmids or SERPINE1 siRNAs on cell apoptosis were evaluated using Hoechst 33258 staining and by detecting expression levels of cleaved caspase-3 using Western blotting.The changes in proliferation of the transfected cells were assessed using EdU and CCK-8 assays.The breast cancer cells with different treatments were co-cultured with macrophages,and M1 and M2 polarization of the macrophages were analyzed with flow cytometry and Western blotting.In nude mouse models bearing subcutaneous breast cancer cell xenografts,the effects of SERPINE1 overexpression and knockdown in the engrafted cells on tumor growth and PTX resistance were evaluated.Results SERPINE1 overexpression significantly inhibited apoptosis and promoted proliferation of MDA-MB-231 cells,and SERPINE1 knockdown obviously promoted apoptosis and inhibited proliferation of MDA-MB-231/PTX cells.The macrophages co-cultured with SERPINE1-overexpressing breast cancer cells showed enhanced M2 polarization and suppressed M1 polarization with a lowered M1/M2 ratio.In the tumor-bearing nude mouse models,SERPINE1 overexpression in the engrafted cells resulted in significantly accelerated tumor growth.Conclusion In MDA-MB-231 cells,SERPINE1 overexpression promotes cell proliferation,inhibits apoptosis,and enhances PTX resistance.SERPINE1 plays a regulatory role in macrophage polarization in the immune microenvironment of breast cancer,and its high expression promotes M2 polarization of the macrophages.关键词
三阴性乳腺癌/丝氨酸蛋白酶抑制剂E1/紫杉醇耐药/肿瘤免疫微环境/M2型巨噬细胞极化Key words
triple-negative breast cancer/serpin family E member 1/paclitaxel resistance/tumor immune microenvironment/M2 macrophage polarization引用本文复制引用
ZHANG Qian,PENG Yanxi,LIU Ze,LIU Bowen,LEI Li,WANG Ye,ZHANG Xinyue,MAO Zhangkun,TANG Peng,ZHANG Jinmei,YANG Jiayi..丝氨酸蛋白酶抑制剂E1过表达通过诱导M2型巨噬细胞极化促进三阴性乳腺癌细胞增殖与紫杉醇耐药[J].南方医科大学学报,2025,45(12):2551-2560,10.基金项目
湖南省自然科学基金区域联合基金项目(2023JJ50412) （2023JJ50412）
湖南省教育厅科学研究重点项目(23A0596) （23A0596）
2024年湖南省大学生创新训练计划项目(4861) （4861）
