目的 探讨泽兰叶黄素调节CXC趋化因子配体12（CXCL12）/CXC趋化因子受体4（CXCR4）信号轴对肺癌细胞增殖、迁移和侵袭的影响。方法 体外培养A549细胞，用不同浓度（0、5、10、20、40、80 mmol/L）泽兰叶黄素处理，筛选药物作用浓度。将细胞分对照组、泽兰叶黄素（10、20、40 mmol/L）组、泽兰叶黄素＋CXCL12组。采用平板克隆法检测A549细胞增殖情况；通过划痕愈合率观察细胞迁移；采用Western blotting法检测CXCL12、CXCR4、G1/S-特异性周期蛋白-D1（CyclinD1）、基质金属蛋白酶（MMP）-2、MMP-9蛋白表达。通过建立裸鼠移植瘤模型，考察泽兰叶黄素对裸鼠移植瘤的生长和组织内相关蛋白表达的影响。结果 选定10、20、40 µmol/L为泽兰叶黄素作用浓度进行后续实验；与对照组比较，泽兰叶黄素组A549细胞克隆率、划痕愈合率和侵袭数目显著下降，CXCL12、CXCR4、CyclinD1、MMP-2、MMP-9蛋白表达显著下调（P＜0.05）；与泽兰叶黄素40 μmol/L组比较，泽兰叶黄素＋CXCL12组细胞克隆率、划痕愈合率和侵袭数目增加，CXCL12、CXCR4、CyclinD1、MMP-2和MMP-9蛋白表达显著上调（P＜0.05）。裸鼠移植瘤实验显示，与对照组比较，泽兰叶黄素组裸鼠移植瘤质量和体积下降，移植瘤组织内CXCL12和CXCR4蛋白表达显著下调（P＜0.05）。结论 泽兰叶黄素可能通过抑制CXCL12/CXCR4信号轴蛋白表达，抑制肺癌细胞增殖、迁移和侵袭速度。

Objective To investigate the effects of eupafolin on proliferation, migration, and invasion of lung carcinoma cells by regulating the CXCL12/CXCR4 signaling axis. Methods A549 cells were cultured in vitro and treated with different concentrations (0, 5, 10, 20, 40, 80 mmol/L) of eupafolin to screen for drug action concentrations. The cells were devided into control group, eupafolin (10, 20, 40 μmol/L) group, and eupafolin + CXCL12 group. Plate cloning method was applied to detect the proliferation of A549 cells. Scratch healing rate was applied to observe cell migration. Western blotting method was applied to detect the protein expression of CXCL12, CXCR4, CyclinD1, MMP-2, and MMP-9. A nude mouse transplantation tumor model was established, and the effects of eupafolin on the growth of nude mouse transplantation tumors, and the expression of tissue related proteins were investigated. Results 10, 20, and 40 µmol/L were selected as the effective concentrations of eupafolin for subsequent experiments. Compared with control group, the cloning rate, scratch healing rate, and invasion number of A549 cells in the eupafolin groups were decreased, the protein expression of CXCL12, CXCR4, CyclinD1, MMP-2, and MMP-9 were downregulated (P < 0.05). Compared with eupafolin 40 µmol/L group, the cloning rate, scratch healing rate, and invasion number of A549 cells in eupafolin + CXCL12 group were increased, and the protein expression of CXCL12, CXCR4, CyclinD1, MMP-2, and MMP-9 were upregulated (P < 0.05). The experiment of nude mouse transplantation showed that compared with the control group, the quality and volume of the transplanted tumor in the eupafolin group decreased, and the expression of CXCL12 and CXCR4 proteins in the transplanted tumor tissue was downregulated (P < 0.05). Conclusion Eupafolin may inhibit the proliferation, migration, and invasion rate of lung carcinoma cells by inhibiting the expression of CXCL12/CXCR4 signaling axis proteins.

R966

邯郸市科学技术研究与发展计划（21422083138）