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

五味子乙素靶向 CDK4/6,通过诱导细胞周期停滞来抑制鼻咽癌的增殖并增强放射敏感性

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

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.

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