目的 探讨色胺酮对人乳腺癌MCF-7细胞的增殖作用及对丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路的影响。方法 将人乳腺癌MCF-7细胞进行体外培养,采用不同浓度色胺酮(0.1,0.5,1,5,10,25,50,100 μmol·L^-1)和ERK,p38MAPK,JNK通路抑制剂处理MCF-7细胞24,48,72 h,MTT法检测细胞增殖活性,Western blot法考察ERK,p-ERK,p38,p-p38,JNK和p-JNK蛋白表达水平。结果 低、中、高剂量色胺酮明显抑制MCF-7细胞增殖活力。不同浓度色胺酮处理MCF-7细胞24,48,72 h时,药物浓度与细胞增殖抑制率呈一定相关性(r=0.904,r=0.793,r=0.770,均P<0.05)。25 μmol·L^-1色胺酮处理MCF-7细胞24 h后显著抑制MCF-7细胞增殖活力(P<0.01); 色胺酮联合ERK抑制剂组、色胺酮联合p38 MAPK抑制剂组、色胺酮联合JNK抑制剂组细胞增殖活力与单用色胺酮组比较差异有统计学意义(P<0.01或P<0.001); 6.25,12.5,25 μmol·L^-1色胺酮处理MCF-7细胞后,p-ERK和p-JNK表达明显增加(P<0.05 或P<0.01);25 μmol·L^-1色胺酮处理MCF-7细胞后p-p38 MAPK表达明显增加(P<0.05);ERK,p38 MAPK,JNK表达均未发现明显变化。结论 色胺酮可抑制MCF-7细胞的增殖活力,且其作用机制可能与MAPK信号通路激活关系密切。

OBJECTIVE To investigate the effect of tryptanthrin on human breast cancer MCF-7 proliferation and MAPK signaling pathway. METHODS The human breast cancer cell MCF-7 was cultured in vitro, different concentrations of 0.1, 0.5, 1, 5, 10, 25, 50, 100 μmol·L^-1 of tryptanthrin and ERK, p38MAPK and JNK pathway inhibitors were used to treat MCF-7 cell for 24, 48 or 72 h. MTT assay was used to detect cell proliferation activity. The expression level of ERK, p-ERK, p38, p-p38, JNK and p-JNK were measured by Western blot method. RESULTS Low, medium and high doses of tryptanthrin significantly inhibited the proliferation of MCF-7 cells. When MCF-7 cells were treated with different concentrations of tryptanthrin for 24, 48, 72 h, the inhibition rate of cell proliferation was correlated with the drug concentration (r=0.904, r=0.793, r=0.770, P<0.05). The 25 μmol·L^-1 of tryptanthrin significantly inhibits the proliferation of MCF-7 cells for 24 h treatment(P<0.01). The cell proliferation activity of tryptanthrin combined with ERK inhibitor group, tryptanthrin combined with p38 MAPK inhibitor group, tryptanthrin combined with JNK inhibitor group was significantly different from that of tryptanthrin group(P<0.01 or P<0.001); MCF-7 cells was treated with 6.25, 12.5, 25 μmol·L^-1 of tryptanthrin, the expression of p-ERK and p-JNK increased significantly(P<0.05 or P<0.01); MCF-7 cells was treated with 25 μmol·L^-1 of tryptanthrin, the expression of p-p38 MAPK increased significantly(P<0.05); the expression of ERK, p38 MAPK and JNK did not change significantly. CONCLUSION Tryptanthrin can inhibit the proliferative activity of MCF-7 cells, and its mechanism may be closely related to the activation of MAPK signaling pathway.