国际肿瘤学杂志 ›› 2012, Vol. 39 ›› Issue (1): 76-79.

• 论著 • 上一篇    

尼美舒利联合顺铂对肺癌细胞增殖与凋亡的影响及其机制探讨

贺利平, 张卿   

  1. 内蒙古医学院附属医院重症医学科
  • 出版日期:2012-01-08 发布日期:2013-11-11
  • 通讯作者: 张卿,E-mail:cfzzhangqing@yahoo.com.cn E-mail:cfzzhangqing@yahoo.com.cn

The effect and mechanism of nimesulide combined with cisplatin on proliferation and apoptosis of lung cancer

HE  Li-Ping, ZHANG  Qing   

  1. Department of Critical Care, Affiliated Hospital Of Inner Mongolia Medical College, Huhhot 010059, China

  • Online:2012-01-08 Published:2013-11-11

摘要: 目的 研究选择性环氧合酶-2(COX-2)抑制剂尼美舒利(NIM)单独以及与顺铂联合对肺癌A549细胞裸鼠移植瘤生长、Ki67及Caspase-3表达的影响,并进一步探讨其机制。方法 将裸鼠用统计学中的依体重按随机数字表法分为4组:对照组、尼美舒利组、顺铂组和联合用药组(尼美舒利+顺铂)。将肺腺癌A549细胞接种至裸鼠皮下,并给予相应的药物治疗21d,观察移植瘤生长情况。免疫组化法检测Caspase-3及Ki67的表达变化。结果 尼美舒利联合顺铂对肺癌裸鼠移植瘤的生长抑制作用较单独用药明显,抑瘤率尼美舒利组为44.33%,顺铂组为53.61%,联合用药组为80.41%(P<0.05)。Caspase-3的表达率在联合用药组(67.43±23.57)%、顺铂组(48.40±20.37)%、尼美舒利组(38.65±15.37)%明显高于对照组(27.63±13.03)% ,P <0.05,联合用药组Caspase-3表达率(67.43±23.57) %高于顺铂组(48.40±20.37) %和尼美舒利组(38.65±15.37%),P <0.05 。Ki67的表达率在联合用药组(24.34±15.90) %、顺铂组(40.85±22.47) %、尼美舒利组(53.33±19.67) %低于对照组(80.43±16.88 ) % ,P <0.05 ,且联合用药组Ki67的表达率(24.34±15.90) %低于顺铂组(40.85±22.47) %和尼美舒利组(53.33±19.67) %,P <0.05。结论 尼美舒利可抑制人肺癌裸鼠移植瘤的生长,与顺铂联合可增强顺铂对肺腺癌A549细胞裸鼠移植瘤的抑制作用,其机制可能与抑制肿瘤细胞Ki67表达,增强Caspase-3表达,抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡有关。

关键词: 肺肿瘤, 顺铂, 细胞增殖, 细胞凋亡, 尼美舒利

Abstract: Objective  To evaluate the effects of selective cyclooxygenase-2 inhibitor nimesulide lone and combined with cisplatin on tumor growth, Ki67 and Caspase-3 expression in lung cancer xenografts in nude mice. Methods  The mice were randomly divided into 4 groups: the control group, the nimesulide group, the cisplatin group and the nimesulide combined with cisplatin group. A549 cells were injected into BALB/c nude mice subcutaneously. On the 21nd day after treatment tumor tissues were collected, and the xenografts growth were observed. The expression of Ki67 and Caspase-3 were detected by immunohistochemical method. Results  Nimesulide combined with cisplatin could significantly inhibited the  xenografts growth compared with nimesulide or cisplatin. The tumor inhibition rate was 44.33% in the nimesulide group, 53.61% in the cisplatin group and 80.41% in the nimesulide combined with cisplatin group (P<0.05). Immunohistochemical analysis showed that the expression rates of caspase-3 was significantly increased in the nimesulide combined with cisplatin group (67.43±23.57)%, the cisplatin group (48.40±20.37)%, and the nimesulide group (38.65±15.37)%, compared with the control group (27.63±13.03)% (P <0.05). The expression rate of Caspase-3 was significantly increased in the nimesulide combined with cisplatin group compared with the nimesulide group or the cisplatin group (P<0.05). The expression rate of Ki67 was significantly decreased in the nimesulide group combined with cisplatin group (24.34±15.90)%, the cisplatin group (40.85±22.47)% and the nimesulide group (53.33±19.67)% compared with the control group (80.43±16.88)% (P<0.05). The expression of Ki67 was significantly decreased in the nimesulide combined with cisplatin group compared with the nimesulide group or the cisplatin group (P <0.05). Conclusion  Nimesulide can inhibit human lung cancer A549 cells xenografts in nude mice growth, Nimesulide enhanced the inhibitory effects of cisplatin. The mechanism may be related to inhibition of tumor cell Ki-67 expression, increased expression of Caspase-3, inhibition of tumor cell proliferation, and inducing tumor cell apoptosis.