【摘要】 目的 探究银杏素（GK）调节丝裂原活化蛋白激酶（MAPK）/激活蛋白-1(AP-1)信号通路对乳腺癌细胞增殖、迁移和侵袭的影响。方法 用不同浓度GK处理人乳腺癌细胞（MCF-7），检测细胞活性，筛选GK浓度；将MCF-7细胞分为对照组（Control组）、GK低浓度组（GK-L组）、GK中浓度组（GK-M组）、GK高浓度组（GK-H组）、GK高浓度+AP-1激活剂ASLAN003组（GK-H+ASLAN003组）；采用平板克隆法检测MCF-7细胞增殖情况；采用流式细胞仪检测MCF-7细胞凋亡情况；通过划痕愈合率来观察MCF-7细胞迁移情况；Transwell小室实验检测MCF-7细胞侵袭情况；采用Wersternblot(WB)法检测MAPK/AP-1信号通路相关蛋白表达；裸鼠移植瘤实验检测GK对乳腺癌移植瘤生长的影响。结果 选择GK浓度为5.0μmol/L、10.0μmol/L、20.0μmol/L用于下一步实验。与Control组比较，GK-L组、GK-M组、GK-H组MCF-7细胞克隆数、划痕愈合率、细胞侵袭数量降低，c-Jun、c-Fos、p-ERK1/2/ERK1/2、p-JNK/JNK、p-p38/p38表达降低，细胞凋亡率升高（P<0.05）；与GK-H组相比，GK-H+ASLAN003组MCF-7细胞克隆数、划痕愈合率、细胞侵袭数量上升，c-Jun、c-Fos、p-ERK1/2/ERK1/2、p-JNK/JNK、p-p38/p38表达上升，细胞凋亡率下降（P<0.05）；与Control组比较，GK组小鼠移植瘤质量和体积显著减小，c-Jun、c-Fos、p-ERK1/2/ERK1/2、p-JNK/JNK、p-p38/p38表达下调（P<0.05）。结论 GK可以抑制MAPK/AP-1通路抑制乳腺癌增殖、迁移和侵袭能力。更多还原

【Abstract】 Objective To explore the effects of ginkgetin(GK) on the proliferation, migration and invasion of breast cancer cells by regulating mitogen-activated protein kinases(MAPK)/activator protein-1(AP-1) signaling pathway. Methods Human breast cancer cells(MCF-7) were treated with different concentrations of GK, the cell activity was detected, and the concentration of GK was screened. MCF-7 cells were divided into Control group, low, medium, and high concentration GK groups(GK-L group, GK-M group, GK-H group), and high concentration GK+AP-1 activator group(GK-H+ASLAN003group). Plate cloning method was applied to detect the proliferation of MCF-7 cells. Flow cytometry was applied to detect the apoptosis of MCF-7 cells. Scratch healing assay was applied to observe the migration of MCF-7 cells. Transwell chamber experiment was applied to detect the invasion of MCF-7 cells. Werstern blot(WB) method was applied to detect the expression of MAPK/AP-1 signaling pathway related proteins. Nude mice transplantation tumor experiment was used to detect the effect of GK on the growth of breast cancer transplantation tumor. Results GK concentrations of 5.0 μmol/L, 10.0 μmol/L, and 20.0 μmol/L were selected for the next experiment. Compared with the Control group, the number of MCF-7 cell clones,scratch healing rate, and number of cell invasions were reduced in the GK-L, GK-M, and GK-H groups, the expression of c-Jun, c-Fos, p-ERK1/2/ERK1/2, p-JNK/JNK, and p-p38/p38 were reduced, the apoptosis rate was increased(P<0.05). Compared with the GK-H group, the number of MCF-7 cell clones, scratch healing rate, and number of cell invasions were increased in the GK-H+ASLAN003 group, the expression of c-Jun, c-Fos, p-ERK1/2/ERK1/2, p-JNK/JNK, and p-p38/p38 were increased, the apoptosis rate was decreased(P<0.05). Compared with the Control group, the weight and volume of transplanted tumors in mice in the GK group were obviously reduced, the expression of c-Jun, c-Fos, p-ERK1/2/ERK1/2,p-JNK/JNK, and p-p38/p38 was down-regulated(P<0.05). Conclusion Ginkgetin can inhibit the proliferation, migration and invasion of breast cancer by inhibiting MAPK/AP-1 pathway.更多还原