• 细胞与分子生物学 • 上一篇    下一篇

冬凌草甲素通过下调XIAP增强吉西他滨对胰腺癌SW1990的抑制作用

周黎明1,卜贺启2,刘殿雷3,金海敏3,周蒙滔4   

  1. 1. 杭州市中医院外一科
    2. 浙江省立同德医院
    3. 杭州市中医院
    4. 温州医科大学附属第一医院
  • 收稿日期:2014-02-11 修回日期:2014-05-18 出版日期:2014-09-15 发布日期:2014-09-15
  • 通讯作者: 周蒙滔

Inhibitory Effects of Oridonin Combined with Gemcitabine on Pancreatic Cancer SW1990Cells

  • Received:2014-02-11 Revised:2014-05-18 Published:2014-09-15 Online:2014-09-15

摘要:

 【摘要】目的探讨冬凌草甲素在体外联合吉西他滨对胰腺癌细胞株SW1990抑制作用及其可能机制。方法 不同浓度的冬凌草甲素(0、10、20、40、80、160μmol/L)作用胰腺癌SW1990细胞24、48、72h后,CCK-8法检测胰腺癌细胞株SW1990细胞的增殖作用;冬凌草甲素(40μmol/L)与吉西他滨(20μmol/L)单独及联合处理细胞48h,并设立对照组, CCK-8法检测SW1990细胞的存活率;Annexin V-FITC/PI双染流式细胞术检测细胞凋亡情况;RTPCR检测SW1990细胞中NF-κB和XIAP基因的表达水平。结果冬凌草甲素对胰腺癌SW1990细胞的增殖抑制作用呈明显的剂量与时间依赖性;与其他各组相比,冬凌草甲素联合吉西他滨组细胞存活率明显降低(P<0.05),凋亡率显著升高(P<0.05);另外,联合组明显下调胰腺癌细胞中NF-κB和XIAP表达水平(P<0.05)。结论冬凌草甲素在体外能显著增强吉西他滨对胰腺癌SW1990细胞的抗瘤效果,其机制可能是通过下调NF-κB及其下游XIAP 的表达,进而诱导胰腺癌细胞的凋亡而实现.

关键词: 冬凌草甲素, 吉西他滨, 胰腺癌, 凋亡, XIAP, NF-κB

Abstract: Object: To investigate whether oridonin can enhance the antitumor effect of gemcitabine on pancreatic cancer SW1990 cells in vitro and explore the potential mechanism of its action. Methods: The pancreatic cancer SW1990 cells were treated with vehicle alone and various concentrations (10、20、40、80、160 μmol/L) of oridonin, followed by 24、48 and 72 h cell culture, Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit; SW1990 cells were treated with oridonin (40 μmol/L) and gemcitabine(20 μmol/L) alone or together for 48 h, with the untreated cells used as the contro1; the survival rate of cells was detected by CCK-8 assay. Apoptosis induction was assessed by using Annexin V-FITC kit; Semi-quantitative RT-PCR was used to examine the changes of NF-κB mRNA and XIAP mRNA expressions. Results: Oridonin inhibited the growth of pancreatic cancer SW1990 cells in a dose- and time-dependent manner. Compared with the other groups, the cell survival rate of the combination group was significantly lowered (P < 0.05). oridonin combined with gemcitabine induced a higher percentage of apoptosis in pancreatic cancer cells than that of oridonin or gemcitabine alone(P <0.05).Moreover, the expressions of NF-κB and XIAP mRNA in pancreatic carcinoma cells were obviously down-regulated in combination group(P <0.05). Conclusion: Oridonin can potentiate the antitumor effect of gemcitabine on pancreatic cancer in vitro, which may be realized through the down-regulation of XIAP and induction of cell apoptosis.

Key words: Oridonin, Gemcitabine, Pancreatic cancer, Apoptosis, XIAP, NF-κB