目的 探讨异戊烯基香豆素类化合物对A549肺癌细胞增殖的影响，并对其构效关系及作用机制进行初步探讨。方法 将人肺癌细胞A549进行体外培养，采用不同浓度异戊烯基香豆素类化合物甘草香豆素（GCM）、甘草酚（GC）、补骨脂定（PSO）、香豆雌酚（COM）、7-去甲基软木花椒素（DE）、7, 2', 4'-trihydroxy-5-methxy-3-penylcoumarin（TMP）和蛇床子素（OST）分别处理肺癌A549细胞36、72 h后，通过结晶紫染色法检测细胞增殖活性；采用蛋白免疫印迹法（Western blotting）检测细胞中TOPK、C-PARP、Bcl-2、Bax、p62、LC3B蛋白表达水平。结果 受试化合物对A549细胞增殖的抑制作用存在浓度和时间相关性；10 μmol/L的GCM、GC、PSO、COM、DE、TMP组Bcl-2表达均下降（P＜0.05）；A549细胞经10 μmol/L GCM、GC、PSO处理后，TOPK的表达显著降低，C-PARP、LC3 Ⅱ、p62的表达显著升高（P＜0.05）。结论 异戊烯基香豆素类化合物GCM、GC、PSO可显著抑制A549细胞的增殖活性，且其抗增殖活性可能与香豆素母核苯环上的异戊烯基结构取代和母核C-3位上苯环的取代及其环上游离的羟基有关；其抗A549细胞增殖的作用机制可能与促进细胞凋亡，诱导细胞发生不完全自噬并抑制自噬流有关。

Objective To explore the influence of prenylated coumarins on the proliferation of lung cancer cells and preliminary explored on its structure-activity relationship and inhibitory mechanism.Methods The human lung cancer cell A549 was cultured in vitro,the cells were treated with different concentrations of Glycycoumarin (GCM),Glycyrol (GC),Psoralidin (PSO),Coumestrol (COM),Demethylsuberosin (DE),7,2',4'-trihydroxy-5-methxy-3-penylcoumarin (TMP),Osthole (OST) for 36 and 72 h.Crystal violet staining was used to detect the activity on the proliferation of A549 cells.Western blotting was used to detect the protein expressions of TOPK,C-PARP,Bcl-2,Bax,p62 and LC3B in the cells.Results The test compounds inhibited the proliferation of A549 cells in a concentration and time-dependent manner.Bcl-2 expression in 10 μmol/L GCM,GC,PSO,COM,DE,TMP groups were decreased (P<0.05).After treatment with 10 μmol/L GCM,GC and PSO,the expression of TOPK in A549 lung cancer cells was significantly decreased,while the expression of C-PARP,LC3II and p62 were significantly increased (P<0.05).Conclusion Prenylated coumarins compound of GCM,GC,PSO can significantly inhibit proliferation activity of A549 cells,and its anti-proliferative activity may be substituted with isoprene structures on coumarin phenylring and mother core.The substitution of the C-3-bit benzene ring is related to the hydroxyl group across the ring,the mechanism of the anti-A549 cell proliferation may be related to the promotion of apoptosis,inducing cells induced by incomplete autophagy and inhibiting autophagy stream.

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贵州省科技计划项目(黔科合支撑[2020]4Y118号);毕节市科技局重点实验室项目(毕科合字[2019]1号)