癌症相关成纤维细胞通过调节NRBP2影响乳腺癌细胞对化疗药物的敏感性。
Cancer-associated fibroblasts affect breast cancer cell sensitivity to chemotherapeutic agents by regulating NRBP2.
作者信息
Jin Xiaoyan, Chen Yong, Wang Gui
机构信息
Department of Surgical Oncology, Taizhou Municipal Hospital, 381 Zhongshan East Road, Jiaojiang District, Taizhou,Zhejiang 318000, China.
Department of General Surgery, Longquan People's Hospital, No. 699, Dongcha Road, Longquan District, Lishui, Zhejiang 323700, China.
出版信息
Toxicol Res (Camb). 2024 Dec 8;13(6):tfae204. doi: 10.1093/toxres/tfae204. eCollection 2024 Dec.
OBJECTIVE
To uncover the role of nuclear receptor-binding protein 2 (NRBP2) in cancer-associated fibroblasts (CAFs), and CAFmediated TAM sensitivity in breast cancer (BC).
METHODS
10 pairs of matched tumor tissues and adjacent normal tissues were collected and CAFs and normal fibroblasts (NFs) were isolated. CCK-8 as well as colony formation assays showed the effects on cell growth. qPCR and Immunoblot showed the expression of NRBP2 in CAFs. FCM as well as Immunoblot assays exhibited the effects on cell apoptosis. Immunoblot further confirmed the mechanism.
RESULTS
CAFs contributed to BC cell growth. In addition, the expression of NRBP2 is downregulated in CAFs. NRBP2 suppressed CAF-induced resistance in BC cells. Further, NRBP2 expression in CAF group increased TAM induced apoptosis. Mechanically, NRBP2 in CAFs inhibited Akt pathway, therefore suppressed resistance in BC cells.
CONCLUSION
CAFs affected BC cell sensitivity to TAM by regulating NRBP2.
目的
揭示核受体结合蛋白2（NRBP2）在癌症相关成纤维细胞（CAF）中的作用，以及CAF介导的乳腺癌（BC）中肿瘤相关巨噬细胞（TAM）敏感性。
方法
收集10对匹配的肿瘤组织和癌旁正常组织，分离CAF和正常成纤维细胞（NF）。CCK-8以及集落形成试验显示对细胞生长的影响。qPCR和免疫印迹显示CAF中NRBP2的表达。流式细胞术以及免疫印迹试验显示对细胞凋亡的影响。免疫印迹进一步证实机制。
结果
CAF促进BC细胞生长。此外，CAF中NRBP2的表达下调。NRBP2抑制CAF诱导的BC细胞耐药。此外，CAF组中NRBP2表达增加TAM诱导的凋亡。机制上，CAF中的NRBP2抑制Akt通路，因此抑制BC细胞中的耐药。
结论
CAF通过调节NRBP2影响BC细胞对TAM的敏感性。
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