乳腺癌是女性中最常见的恶性肿瘤。多柔比星（Dox）耐药是改善乳腺癌患者临床结果的主要障碍之一。本研究旨在探讨FABP信号通路与乳腺癌多柔比星耐药之间的关系。利用CCK-8、Western blot（WB）和共聚焦显微镜技术评估MCF-7/ADR细胞的耐药特性。利用透射电子显微镜、PAS和Oil Red O染色技术鉴定MCF-7和MCF-7/ADR细胞的糖脂代谢特性。通过GEO和WB方法评估FABP5和CaMKII的表达水平。利用流式细胞仪测定细胞内钙离子水平。通过免疫组织化学评估临床乳腺癌患者的肿瘤组织，确定FABP5和p-CaMKII蛋白的表达情况。在存在或缺乏FABP5 siRNA或FABP5特异性抑制剂SBFI-26的情况下，利用CCK-8、WB和集落形成方法研究多柔比星耐药，并检测细胞内钙离子水平。通过分子对接分析探究多柔比星的结合能力。结果表明，我们所使用的MCF-7/ADR细胞是多柔比星耐药的MCF-7细胞。与母细胞MCF-7相比，MCF-7/ADR细胞中FABP5的表达明显增加。在耐药患者中，FABP5和p-CaMKII的表达比敏感个体中增加。通过siRNA或抑制剂抑制FABP5蛋白的表达，可提高MCF-7/ADR细胞对多柔比星的敏感性，降低细胞内钙离子、PPARγ和自噬水平。分子对接结果显示，与已知与耐药相关的蛋白P-GP相比，FABP5与多柔比星的结合能力更强。总之，FABP5介导的PPARγ和CaMKII轴在乳腺癌化疗耐药中发挥关键作用。FABP5是一种潜在可靶向的蛋白和乳腺癌多柔比星耐药治疗的治疗生物标记物。版权所有©2023陈，马，苗，张，韩，阿尔玛马里，黄，陈，刘和苏。

Breast cancer is the most prevalent malignancy among women. Doxorubicin (Dox) resistance was one of the major obstacles to improving the clinical outcome of breast cancer patients. The purpose of this study was to investigate the relationship between the FABP signaling pathway and Dox resistance in breast cancer. The resistance property of MCF-7/ADR cells was evaluated employing CCK-8, Western blot (WB), and confocal microscopy techniques. The glycolipid metabolic properties of MCF-7 and MCF-7/ADR cells were identified using transmission electron microscopy, PAS, and Oil Red O staining. FABP5 and CaMKII expression levels were assessed through GEO and WB approaches. The intracellular calcium level was determined by flow cytometry. Clinical breast cancer patient's tumor tissues were evaluated by immunohistochemistry to determine FABP5 and p-CaMKII protein expression. In the presence or absence of FABP5 siRNA or the FABP5-specific inhibitor SBFI-26, Dox resistance was investigated utilizing CCK-8, WB, and colony formation methods, and intracellular calcium level was examined. The binding ability of Dox was explored by molecular docking analysis. The results indicated that the MCF-7/ADR cells we employed were Dox-resistant MCF-7 cells. FABP5 expression was considerably elevated in MCF-7/ADR cells compared to parent MCF-7 cells. FABP5 and p-CaMKII expression were increased in resistant patients than in sensitive individuals. Inhibition of the protein expression of FABP5 by siRNA or inhibitor increased Dox sensitivity in MCF-7/ADR cells and lowered intracellular calcium, PPARγ, and autophagy. Molecular docking results showed that FABP5 binds more powerfully to Dox than the known drug resistance-associated protein P-GP. In summary, the PPARγ and CaMKII axis mediated by FABP5 plays a crucial role in breast cancer chemoresistance. FABP5 is a potentially targetable protein and therapeutic biomarker for the treatment of Dox resistance in breast cancer.Copyright © 2023 Chen, Ma, Miao, Zhang, Han, Almaamari, Huang, Chen, Liu and Su.