吴茱萸碱对人胰腺癌SW1990细胞株体内外增殖及凋亡的影响

摘要

Objective: To investigate the effects of Evodiamine on the proliferation and apoptosis of pan-creatic cancer SW1990 cells. Methods: Pancreatic cancer SW1990 cells were mixed with different concentra-tions of Evodiamine (0, 5, 10, 20, 40, 80 μmol/L) after 12, 24, 48 hours respectively. The SW1990 cells' prolif-eration was detected by cell counting Kit-8 (CCK-8). The SW1990 cells' cycle was detected with flow cytometry test. Nude mouse models were established with orthotopic transplantation tumor, which were injected with differ-ent concentrations of Evodiamine for 2 weeks. The orthotopic transplantation tumor's weight was measured after sacrificed. The expression of Active Caspase-3 and Active Caspase-8 in tumor tissues was detected by Western blot and immunohistochemistry. Results: Evodiamine inhibited the proliferation effect of SW1990 cells by con-centration and time dependence. The quantity of pancreatic cancer SW1990 cells in G2/M phase significantly increased. The expressions of Active Caspase-3 and Active Caspase-8 protein significantly increased. With in-creasing of Evodiamine concentrations, the inhibiting effect on the nude mouse's growth of pancreas transplanta-tion tumor was more remarkable and the expressions of Active Caspase-3 and Active Caspase-8 increased much more obviously in the tumor tissues. Conclusion: Evodiamine can significantly inhibit human pancreatic cancer SW1990 cells' proliferation with concentration and time dependence. Its mechanism may retard the growth of pancreatic cancer cells in G2/M phase. In the meantime, Evodiamine can activate Caspase-8 and Caspase-3, then promote the apoptosis of pancreatic cancer cells.%目的:通过体内外实验探讨吴茱萸碱对人胰腺癌SW1990细胞株增殖及凋亡的影响.方法:人胰腺癌细胞株SW1990在经0、5、10、20、40、80μmol/L吴茱萸碱分别作用12、24、48 h后,应用CCK-8法检测吴茱萸碱对SW1990细胞的增殖抑制作用;流式细胞术检测吴茱萸碱对SW1990细胞周期的影响;Western blot检测SW1990细胞中Active Caspase-3及Active Caspase-8的表达.建立裸鼠胰腺癌原位移植瘤模型,分别予以0、10、20、30 mg/kg吴茱萸碱腹腔注射处理2周,每周给药3次后,观察裸鼠生长情况;处死裸鼠后,检测原位移植瘤重的变化;Western blot及免疫组织化学法检测肿瘤组织中Active Caspase-3及Active Caspase-8的表达.结果:吴茱萸碱对SW1990细胞的增殖抑制作用呈浓度和时间依赖性;胰腺癌SW1990细胞在G2/M期的细胞数明显增加;Western blot检测示SW1990细胞中Active Caspase-3及Active Caspase-8蛋白的表达明显升高.在体内,随着吴茱萸碱浓度的增加,对裸鼠原位胰腺移植瘤的生长抑制更明显,瘤体中Active Caspase-3及Active Caspase-8蛋白的表达明显升高.结论:吴茱萸碱可显著抑制人胰腺癌SW1990细胞增殖,其作用在一定时间内呈浓度和时间依赖性,作用机制可能是将胰腺癌细胞的生长阻滞在G2/M期.同时吴茱萸碱可激活Caspase-8,并活化其下游的Caspase-3,从而促进肿瘤细胞的凋亡.