目的 探讨石蒜碱通过激活微管相关基因STMN1阻滞人乳腺癌MCF-7细胞周期相关分子机制。方法 MCF-7细胞给予石蒜碱干预后，采用CCK-8法检测细胞增殖抑制率；流式细胞术检测G₂/M期细胞比例、磷酸化组蛋白H3（phosphorylated histone H3，p-H3）表达；荧光显微镜观察石蒜碱对MCF-7细胞微管形态的影响；qRT-PCR检测MCF-7细胞周期、骨架及微管相关基因的表达；Western blotting检测MCF-7细胞内5个周期阻滞相关蛋白的表达。结果 石蒜碱对MCF-7细胞的半数抑制浓度（half inhibitory concentration，IC₅₀）为13.98 μmol/L。石蒜碱呈剂量相关性地将MCF-7细胞阻滞于G₂/M期（P＜0.01），并增加p-H3表达（P＜0.05、0.01）。当石蒜碱浓度为28 µmol/L时，细胞微管形态接近于阳性对照药物长春新碱。石蒜碱可下调5个信号传导相关基因，上调2个微管相关基因，下调2个M期相关基因，进而下调5个周期阻滞相关蛋白。相关性分析表明石蒜碱通过激活微管相关基因STMN1，导致微管动态平衡被破坏，最终导致M期阻滞。抑制STMN1基因后，石蒜碱无法将MCF-7细胞周期阻滞在M期。结论 石蒜碱抑制MCF-7细胞增殖并通过促进微管解聚将其阻滞于M期，且阻滞M期的关键位点是基因STMN1，为未来药物设计和癌症治疗策略的探索提供了有价值的信息。

Objective To investigate the molecular mechanism of lycorine blocking MCF-7 cell cycle through activating microtubule-associated gene STMN1. Methods After intervention with lycorine on MCF-7 cells, cell proliferation inhibition rate was measured by CCK-8 assay; The proportion of cells in G₂/M phase and phosphorylated histone H3 (p-H3) expression were detected by flow cytometry; The effect of lycorine on microtubule morphology of MCF-7 cells was observed by fluorescence microscopy; The expressions of MCF-7 cell cycle, skeleton and microtubule related genes were detected by qRT-PCR; Western blotting was employed to detect the expressions of five cycle arrest related proteins in MCF-7 cells. Results The half inhibitory concentration (IC₅₀) of lycorine in MCF-7 cells was 13.98 μmol/L. Lycorianine inhibited MCF-7 cells in G₂/M phase (P < 0.01) and increased p-H3 expression (P < 0.05, 0.01) in a dose-dependent manner. When the concentration of lycorine was 28 µmol/L, the microtubule morphology of cells was similar to that of the positive control drug vincristine. Lycorine down-regulated five signal transduction-related genes, up-regulated two microtubule-related genes, down-regulated two M phase-related genes, and subsequently down-regulated five cell cycle arrest-related proteins. Correlation analysis indicated that lycorine could disrupt microtubule homeostasis by activating microtubule related gene STMN1, and eventually lead to M-phase arrest. After inhibiting STMN1 gene, lycorine could not block MCF-7 cell cycle in M phase. Conclusion Lycorine effectively inhibits the proliferation of MCF-7 cells and induces M-phase arrest by promoting microtubule depolymerization, with the STMN1 gene being key point of M-phase blockade. This study provides valuable basic information for future drug design and exploration of cancer treatment strategies.

R285.5

黑龙江省重点研发项目（2022ZX02C07）；黑龙江省普通高等学校青年创新人才培养计划项目（UNPYSCT-2020218）；哈尔滨商业大学2023年研究生创新科研基金项目（YJSCX2023-785HSD）；2023年度哈尔滨商业大学镜湖学者支持计划项目（JHQNRC06）；哈尔滨商业大学博士科研支持计划项目（24BQ31）