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五味子乙素通过诱导细胞周期停滞靶向细胞周期蛋白依赖性激酶4/6,抑制鼻咽癌增殖并增强其放射敏感性。

Schisandrin B targets CDK4/6 to suppress proliferation and enhance radiosensitivity in nasopharyngeal carcinoma by inducing cell cycle arrest.

作者信息

Fang Yanhua, Lv Xinhui, Li Ge, Wang Piao, Zhang Lingling, Wang Ruoyu, Jia Lingyun, Liang Shanshan

机构信息

Liaoning Key Laboratory of Molecular Recognition and Imaging, School of Bioengineering, Dalian University of Technology, Dalian, 116024, China.

The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Affiliated Zhongshan Hospital of Dalian University, No.6 Jiefang Street, Zhongshan District, Dalian, 116001, Liaoning, China.

出版信息

Sci Rep. 2025 Mar 12;15(1):8452. doi: 10.1038/s41598-025-92992-9.

DOI:10.1038/s41598-025-92992-9
PMID:40069371
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11897163/
Abstract

Nasopharyngeal carcinoma (NPC) is notably prevalent in East and Southeast Asia, where despite advancements in radiotherapy leading to high control rates, challenges like radioresistance and collateral tissue damage remain significant. While Schisandrin B (SchB) has been demonstrated antitumor effects in various tumors, its efficacy in NPC remains unexplored. In this study, we explored the antitumor potential of Sch B on NPC, particularly its effects on cell proliferation and radiosensitivity. Our research demonstrates that Sch B effectively inhibits the proliferation of NPC cell lines HONE-1 and CNE-1 by inducing cell cycle G1 phase arrest, specifically through the down-regulation of cyclin-dependent kinase 4/6, without impacting the normal nasopharyngeal epithelial cell line NP69. This selective inhibitory effect positions Sch B as a targeted therapeutic agent, sparing healthy tissue from adverse effects. Furthermore, we observed that Sch B enhances the efficacy of radiotherapy in NPC cells by obstructing DNA double-strand break repair mechanisms, suggesting that a combined treatment regimen of Sch B and radiation could offer a superior therapeutic strategy. These findings propose Sch B not only as a potent inhibitor of NPC cell proliferation but also as an enhancer of radiosensitivity, providing a promising avenue for improving NPC treatment outcomes.

摘要

鼻咽癌(NPC)在东亚和东南亚地区尤为普遍,尽管放射治疗取得了进展,控制率较高,但诸如放射抗性和周围组织损伤等挑战仍然很严峻。虽然五味子乙素(SchB)已在多种肿瘤中显示出抗肿瘤作用,但其在鼻咽癌中的疗效仍未得到探索。在本研究中,我们探究了SchB对鼻咽癌的抗肿瘤潜力,特别是其对细胞增殖和放射敏感性的影响。我们的研究表明,SchB通过诱导细胞周期G1期阻滞,特别是通过下调细胞周期蛋白依赖性激酶4/6,有效抑制鼻咽癌HONE-1和CNE-1细胞系的增殖,而不影响正常鼻咽上皮细胞系NP69。这种选择性抑制作用使SchB成为一种靶向治疗药物,使健康组织免受不良反应的影响。此外,我们观察到SchB通过阻碍DNA双链断裂修复机制增强了放射治疗对鼻咽癌细胞的疗效,这表明SchB与放疗的联合治疗方案可能提供一种更优的治疗策略。这些发现表明,SchB不仅是鼻咽癌增殖的有效抑制剂,也是放射敏感性的增强剂,为改善鼻咽癌的治疗效果提供了一条有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/234b2abbbcb7/41598_2025_92992_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/e11a3f8c9ae8/41598_2025_92992_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/fd15d28a6848/41598_2025_92992_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/91b5f22d8b4f/41598_2025_92992_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/111f1861aae2/41598_2025_92992_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/234b2abbbcb7/41598_2025_92992_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/e11a3f8c9ae8/41598_2025_92992_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/fd15d28a6848/41598_2025_92992_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/91b5f22d8b4f/41598_2025_92992_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/111f1861aae2/41598_2025_92992_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939c/11897163/234b2abbbcb7/41598_2025_92992_Fig5_HTML.jpg

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