吴茱萸碱对人胰腺癌SW1990细胞株体内外增殖及凋亡的影响  

The effects of Evodiamine on the proliferation and apoptosis of pancreatic cancer SW1990 cells in vivo and in vitro

作　　者：陈辉[1] 王兆洪[1] 陈龙[1] 范恒伟[1] 周斌[1] 徐鲁白[1] 童洪飞[1] CHEN Hui WANG Zhaohong CHEN Long FAN Hengwei ZHOU Bin XU Lubai TONG Hongfei.(Department of Hepatobiliary, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 32502)

机构地区：[1]温州医科大学附属第二医院肝胆胰外科,浙江温州325027

出　　处：《温州医科大学学报》2017年第6期431-434,440,共5页Journal of Wenzhou Medical University

基　　金：浙江省中医药管理局青年基金资助项目(2014ZQ020);温州市公益性科技计划项目(Y20140694)

摘　　要：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。Objective： To investigate the effects of Evodiamine on the proliferation and apoptosis of pancreatic cancer SW1990 cells. Methods： Pancreatic cancer SW1990 cells were mixed with different concentrations of Evodiamine （0, 5, 10, 20, 40, 80 μmol/L） after 12, 24, 48 hours respectively. The SW1990 cells＇ proliferation 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 concentration 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 increasing of Evodiamine concentrations, the inhibiting effect on the nude mouse＇s growth of pancreas transplantation 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.

关 键 词：吴茱萸碱 胰腺癌 细胞增殖 细胞凋亡 细胞周期 Caspase.3 Caspase.8 

分 类 号：R735.9[医药卫生—肿瘤]