Cancer-associated fibroblasts affect breast cancer cell sensitivity to chemotherapeutic agents by regulating NRBP2.

IF 2.2 4区 医学 Q3 TOXICOLOGY Toxicology Research Pub Date : 2024-12-08 eCollection Date: 2024-12-01 DOI:10.1093/toxres/tfae204
Xiaoyan Jin, Yong Chen, Gui Wang
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Abstract

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.

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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。
目的:揭示核受体结合蛋白2 (NRBP2)在癌症相关成纤维细胞(CAFs)中的作用,以及CAFs介导的TAM在乳腺癌(BC)中的敏感性。方法:收集10对匹配的肿瘤组织和邻近正常组织,分离成纤维细胞和正常成纤维细胞。CCK-8和菌落形成试验显示了对细胞生长的影响。qPCR和免疫印迹显示NRBP2在cas中表达。流式细胞仪和免疫印迹检测显示其对细胞凋亡的影响。免疫印迹进一步证实了其作用机制。结果:CAFs促进了BC细胞的生长。此外,NRBP2在cas中的表达下调。NRBP2抑制caf诱导的BC细胞耐药。此外,CAF组NRBP2表达增加了TAM诱导的细胞凋亡。机制上,CAFs中的NRBP2抑制Akt通路,从而抑制BC细胞的耐药。结论:CAFs通过调控NRBP2影响BC细胞对TAM的敏感性。
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来源期刊
Toxicology Research
Toxicology Research TOXICOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
82
期刊介绍: A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology
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