Lv Meng, Chen Xiangrui, Yang Qiting, Huang Chushuan, Lv Yongbiao, Zhang Tian, Cai Junxiang
Department of Respiratory and Critical Care Medicine, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, China.
Department of Hematology and Oncology, Third People's Hospital of Zigong, Zigong, Sichuan, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 4. doi: 10.1007/s00210-024-03729-w.
Berberine (BBR) has been proved to inhibit the malignant progression of non-small cell lung cancer (NSCLC), but the underlying molecular mechanism still needs to be further revealed. NSCLC cells (A549 and H1299) were treated with BBR. CCK8 assay, colony formation assay, flow cytometry, TUNEL staining and transwell assay were used to examine cell proliferation, apoptosis and invasion. The levels of spindle pole body component 25 (SPC25) and NDC80 kinetochore complex component (NUF2) were detected by qRT-PCR or western blot. The interaction between SPC25 and NUF2 was confirmed by Co-IP assay and FISH assay. Xenograft tumors were constructed to assess the anti-tumor role of BBR in vivo. BBR inhibited NSCLC cell growth, invasion and glycolysis. SPC25 was upregulated in NSCLC tissues, and BBR could reduce SPC25 expression in NSCLC cells. SPC25 knockdown repressed NSCLC cell growth, invasion and glycolysis, and its overexpression also reversed the anti-tumor effect of BBR. SPC25 could interact with NUF2, and NUF2 overexpression abolished the inhibitory effect of SPC25 knockdown or BBR on NSCLC cell behaviors. In animal experiments, BBR could suppress NSCLC tumor growth by inhibiting SPC25/NUF2 axis in vivo. BBR mainly played an anti-NSCLC role by targeting SPC25/NUF2 axis, which provided a new idea for NSCLC treatment.
黄连素（BBR）已被证明可抑制非小细胞肺癌（NSCLC）的恶性进展，但其潜在的分子机制仍有待进一步揭示。用BBR处理NSCLC细胞（A549和H1299）。采用CCK8法、集落形成法、流式细胞术、TUNEL染色和Transwell法检测细胞增殖、凋亡和侵袭情况。通过qRT-PCR或蛋白质免疫印迹法检测纺锤极体成分25（SPC25）和NDC80动粒复合体成分（NUF2）的水平。通过免疫共沉淀法和荧光原位杂交法证实SPC25与NUF2之间的相互作用。构建异种移植瘤以评估BBR在体内的抗肿瘤作用。BBR抑制NSCLC细胞生长、侵袭和糖酵解。SPC25在NSCLC组织中上调，BBR可降低NSCLC细胞中SPC25的表达。敲低SPC25可抑制NSCLC细胞生长、侵袭和糖酵解，其过表达也可逆转BBR的抗肿瘤作用。SPC25可与NUF2相互作用，过表达NUF2可消除敲低SPC25或BBR对NSCLC细胞行为的抑制作用。在动物实验中，BBR可通过在体内抑制SPC25/NUF2轴来抑制NSCLC肿瘤生长。BBR主要通过靶向SPC25/NUF2轴发挥抗NSCLC作用，这为NSCLC治疗提供了新思路。
