中国普通外科杂志2025，Vol.34Issue(11)：2380-2388,9.DOI:10.7659/j.issn.1005-6947.240612
CXCR4/CXCR7与NF-κB通路在三阴性乳腺癌中的关联及功能研究
Association and functional role of CXCR4/CXCR7 and the NF-κB pathway in triple-negative breast cancer
摘要
Abstract
Background and Aims:Triple-negative breast cancer(TNBC)is highly aggressive and lacks effective targeted therapies.The chemokine receptors CXCR4 and CXCR7 are overexpressed in TNBC and may promote tumour cell migration and invasion by activating the NF-κB signalling pathway.This study aimed to investigate the roles of CXCR4/CXCR7 and the NF-κB pathway in regulating the migration and invasion of TNBC cells. Methods:In the TNBC cell line MDA-MB-231,CRISPR/Cas9 technology was used to individually or in combination knock out the CXCR4 and CXCR7 genes.Additionally,a group treated with the NF-κB inhibitor BAY 11-7082 was established.The phosphorylation levels of IκB-α and p65 were assessed by Western blotting to evaluate NF-κB pathway activity.Cell proliferation,migration,and invasion were evaluated using the CCK-8 assay,wound healing assay,and Transwell assay,respectively. Results:MDA-MB-231 cell lines with CXCR4,CXCR7,or dual gene knockout were successfully established.Western blot analysis revealed that the phosphorylation levels of IκB-α and p65 were significantly reduced in all knockout groups(all P<0.05),with the dual knockout group exhibiting a more substantial inhibitory effect than the single knockouts.However,BAY 11-7082(5 μmol/L,24 h)exerted a more pronounced suppression of IκB-α and p65 phosphorylation compared to the dual knockout group(all P<0.05).Functional assays demonstrated that both gene knockout and NF-κB inhibition significantly impaired the migration and invasion of TNBC cells(all P<0.05).Among all groups,the dual knockout of CXCR4 and CXCR7 showed greater inhibitory effects than either single knockout.At the same time,the BAY 11-7082 treatment exhibited the most potent suppression of both migration and invasion(both P<0.05). Conclusion:CXCR4 and CXCR7 promote TNBC cell migration and invasion by activating the NF-κB signalling pathway,suggesting that the NF-κB pathway may serve as a potential therapeutic target for combination immunotherapy in TNBC.关键词
三阴性乳腺癌/受体,CXCR/NF-κB/肿瘤浸润Key words
Triple Negative Breast Neoplasms/Receptors,CXCR/NF-κB/Neoplasm Invasiveness分类
医药卫生引用本文复制引用
李珮婷,曾宸,吴润柳,杨萌,李俊,周建大,吴唯..CXCR4/CXCR7与NF-κB通路在三阴性乳腺癌中的关联及功能研究[J].中国普通外科杂志,2025,34(11):2380-2388,9.基金项目
湖南省自然科学基金资助项目(2018JJ2610) （2018JJ2610）
北京生命绿洲公益服务中心基金资助项目(cphcf-2023-046). （cphcf-2023-046）
