目的 研究蝙蝠葛碱对肝癌Huh7细胞增殖和凋亡的作用，探索其抗肿瘤的作用机制和与Hedgehog信号通路的关系。方法 不同质量浓度（2、4、8 μg/mL）的蝙蝠葛碱处理Huh7细胞，采用四甲基偶氮唑蓝（MTT）法检测Huh7细胞增殖能力的变化；流式细胞术分析细胞凋亡；real-time PCR、Western blotting法检测Hedgehog信号通路相关基因及蛋白表达水平。结果 随着蝙蝠葛碱质量浓度及作用时间的增加，其对Huh7细胞增殖的抑制率升高。其中蝙蝠葛碱8 μg/mL作用48 h对细胞增殖抑制率最高（48.8%）。蝙蝠葛碱可明显诱导Huh7细胞发生凋亡。随着蝙蝠葛碱质量浓度的增大，细胞的凋亡率显著升高（P<0.05、0.01）。与对照组比较，蝙蝠葛碱各质量浓度组细胞Hedgehog信号通路中PTCH1、GLi1、SMO、SHH mRNA和蛋白表达水平显著降低，同时cleaved Caspase-3蛋白水平显著升高，而Bcl-2表达水平降低（P<0.05、0.01），并呈质量浓度依赖性。结论 蝙蝠葛碱可明显抑制Huh7细胞的增殖，促进其凋亡，其可能通过抑制Hedgehog信号通路发挥作用。

Objective To study the effect of dauricine on the proliferation and apoptosis of hepatoma Huh7 cells, and explore its anti-tumor mechanism and its relationship with Hedgehog signaling pathway. Methods The effects of different concentrations of dauricine (2, 4, 8 μg/mL) on the proliferation of Huh7 cells were detected by MTT assay. Apoptosis of Huh7 cells was analyzed by flow cytometry. Real-time PCR and Western blotting were used to detect the levels of Hedgehog signaling pathway-related genes and proteins. Results With the increase of the concentration of dauricine and the duration of action, the inhibition rate of Huh7 cell proliferation was increased. Among them, 8 μg/mL dauricine had the highest inhibition rate (48.8%) at 48 h. Dauricine induced the apoptosis in Huh7 cells. With the increase of the concentration of dauricine, the apoptotic rate of cells was increased significantly (P < 0.05, 0.01). The mRNA and protein expression levels of PTCH1, GLi1, SMO and SHH genes in Hedgehog signaling pathway were significantly decreased, while the level of cleaved Caspase-3 protein was significantly increased, accompany with the decreased expression of Bcl-2 in dauricine concentration-dependent pattern (P < 0.05, 0.01) in dauricine group compared with the control group. Conclusion Dauricine could significantly inhibit the proliferation and promote apoptosis of Huh7 cells, which may play a role by blocking Hedgehog signaling pathway.

河南省自然科学基金资助项目（162300410289）