空军军医大学学报2025，Vol.46Issue(7)：887-894,8.DOI:10.13276/j.issn.2097-1656.2025.07.007
内质网应激调控乳腺癌细胞对多柔比星耐药的机制研究
Mechanism of endoplasmic reticulum stress regulating doxorubicin resistance in breast cancer cells
摘要
Abstract
Objective To explore the mechanism of endoplasmic reticulum stress(ERS)in doxorubicin(DOX)resistance in breast cancer cells and provide theoretical support for clinical treatment.Methods Triple-negative breast cancer cells(MDA-MB-231,HCC1937)and non-triple-negative breast cancer cells(MCF-7,T47D)were taken as research subjects,parental cells(MDA-MB-231,MCF-7)as the control group,and the constructed DOX-resistant cell lines(MDA-MB-231/ADR,MCF-7/ADR)as the experimental group.The expression levels of ERS-related molecules were detected by RNA-Seq analysis,qRT-PCR,Western blotting and other methods.The impact of different ERS pathways on DOX sensitivity in breast cancer cells was investigated through inhibitor drug combination experiments(DOX combined with IRE1α inhibitor Kira6 or PERK inhibitor GSK2606414)and the construction of stable cell lines(MDA-MB-231 cell lines with XBP1 knockdown).Results The study found that the endoplasmic reticulum protein processing pathway was significantly enriched in different breast cancer cell lines,and the drug resistance mechanisms varied among different cell lines(P＜0.05).In triple-negative breast cancer cell lines,activation of the IRE1α-XBP1 pathway promoted DOX resistance by enhancing cellular autophagy levels.Conversely,in non-triple-negative breast cancer cell lines,activation of the PERK pathway played a critical role.Conclusion This study reveals the significant role of ERS in DOX resistance of breast cancer and provides a theoretical basis and potential targets for the targeted development of therapeutic strategies to reverse DOX resistance in breast cancer.关键词
内质网应激/乳腺癌/多柔比星/药物耐药性/三阴性乳腺癌/自噬/未折叠蛋白反应/肿瘤细胞系Key words
endoplasmic reticulum stress/breast cancer/doxorubicin/drug resistance/triple-negative breast cancer/autophagy/unfolded protein response/tumor cell line分类
医药卫生引用本文复制引用
孙佳宁,汪家佳,樊聪,贾林涛,王廷,张健..内质网应激调控乳腺癌细胞对多柔比星耐药的机制研究[J].空军军医大学学报,2025,46(7):887-894,8.基金项目
国家自然科学基金(82372960) （82372960）
陕西省创新能力支撑计划科技创新团队项目(2023-CX-TD-67,2022TD-47) （2023-CX-TD-67,2022TD-47）
