目的 探讨藁本内酯调节缺氧诱导因子-1α（HIF-1α）/神经源性基因Notch同源蛋白1（Notch1）信号通路对口腔鳞状细胞癌细胞增殖、凋亡和上皮–间质转化的影响。方法 将CAL-27细胞分为对照组、藁本内酯（25、50、100 μmol/L）组、顺铂组、藁本内酯＋HIF-1α激活剂（CoCl₂）组。通过CCK-8、克隆形成、流式细胞术、Transwell小室实验、划痕实验评估细胞功能；Western blotting检测增殖细胞核抗原（PCNA）、细胞周期蛋白D1（Cyclin D1）、B细胞淋巴瘤-2（Bcl-2）、裂解的胱天蛋白酶-3（cleaved Caspase-3）、Bcl-2相关X蛋白（Bax）、E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）、波形蛋白（Vimentin）、蜗牛家族转录抑制因子（Snail）、HIF-1α、Notch1蛋白表达情况。结果 藁本内酯可显著降低CAL-27细胞存活率（P＜0.05），半数抑制浓度（IC₅₀）为99.67 μmol/L，且对正常Hacat细胞无明显毒性。体外实验表明，藁本内酯能显著抑制细胞增殖、迁移、侵袭并诱导凋亡，同时下调PCNA、Cyclin D1、N-cadherin、Vimentin、Snail、HIF-1α及Notch1蛋白表达，上调cleaved Caspase-3、Bax/Bcl-2及E-cadherin蛋白表达（P＜0.05），且呈浓度相关性。CoCl₂可逆转藁本内酯对上述指标的调控作用。结论 藁本内酯可能通过抑制HIF-1α/Notch1通路抑制口腔鳞状细胞癌细胞增殖和上皮–间质转化进程，并诱导细胞凋亡。

Objective To investigate the effect of ligustilide on the proliferation, apoptosis, and epithelial-mesenchymal transition of oral squamous cell carcinoma cells by regulating HIF-1α/Notch1 signaling pathway. Methods CAL-27 cells were divided into the control group, ligustilide (25, 50, and 100 μmol/L) group, cisplatin group, and ligustilide + HIF-1α activator (CoCl₂) group. Cellular functions were evaluated using CCK-8, colony formation, flow cytometry, Transwell, and wound healing assays, and the protein levels of PCNA, Cyclin D1, Bcl-2, Cleaved Caspase-3, Bax, E-cadherin, N-cadherin, Vimentin, Snail, HIF-1α, and Notch1 were determined by Western blotting. Results Ligustilide inhibited the survival rate of CAL-27 cells, IC₅₀ was 99.67 μmol/L, while showing no significant cytotoxicity toward normal Hacat cells. In vitro experiments demonstrated that ligustilide significantly suppressed proliferation, migration, and invasion, and induced apoptosis of CAL-27 cells. It also downregulated the protein levels of PCNA, Cyclin D1, N-cadherin, Vimentin, Snail, HIF-1α, and Notch1, while upregulated cleaved Caspase-3, Bax/Bcl-2 and E-cadherin (P < 0.05), and it shows a concentration-related pattern. The regulatory effects of ligustilide on the aforementioned indicators were reversed by CoCl₂. Conclusion Ligustilide may inhibit the proliferation and epithelial-mesenchymal transition process of oral squamous cell carcinoma cells and induce cell apoptosis by suppressing the HIF-1α/Notch1 pathway.

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郑州大学第一附属医院学科培育项目（2025XKPY020）