COX-2抑制剂对肺癌裸鼠移植瘤血管生成素基因表达的影响

Influence of COX-2 inhibitor on angiopoietin expression of human lung cancer xenografts in nude mice

目的:探讨环氧化酶-2(COX-2)抑制剂尼米舒利(NIM)对肺癌裸鼠移植瘤的血管生成素基因表达的影响及意义。方法:人肺癌A549细胞接种于裸鼠皮下,建立肺癌裸鼠移植瘤模型并予NIM治疗,计算NIM的抑瘤率,RT-PCR检测裸鼠移植瘤组织血管生成素-1、2(Ang-1、Ang-2)mRNA表达,免疫组织化学法测定裸鼠移植瘤组织微血管密度(MVD)。结果:NIM可有效抑制裸鼠移植瘤的生长,其抑瘤率为43.02%。NIM治疗组裸鼠移植瘤组织Ang-2mRNA水平显著低于对照组(P<0.01),Ang-1mRNA水平无显著改变(P>0.05),Ang-2/Ang-1mRNA比值下降(P<0.01);同时MVD明显低于对照组(P<0.01)。结论:COX-2抑制剂NIM可下调Ang-2基因表达,改变Ang-2/Ang-1mRNA比值,该作用可能是COX-2抑制剂抑制肿瘤血管生成从而抑制肿瘤生长的机制之一。

AIM： To investigate the influence and significance of nimesulide （NIM）, a selective cyclooxygenase 2 （COX- 2） inhibitor, on angiopoietin expression of human lung cancer xenografts in nude mice. METHODS： Human A549 lung cancer cells were inoculated subcutaneously in athymic nude mice to establish xenograft models. The mice were divided into NIM group and control group randomly. Mice in NIM group and control group were administered with NIM （6 mg/kg） and saline into stomachs respectively once a day for 35 days. The inhibitory rate was calculated and expressions of angiopoietin - 1, - 2 （ Ang - 1, Ang-2） mRNA in xenografts were measured by semiquantitative reverse transcription- polymerase chain reaction （RT- PCR） analysis. Microvessel density （MVD） in xenografts was assessed immunohistochemically using antibody against FⅦ. RESULTS： NIM inhibited the xenografts growth significantly and the inhibitory rate was 43.02%. Expression of Ang- 2 mRNA but not Ang - 1 mRNA was significantly reduced （ P 〈 0.01 ） ,thus Ang - 2/Ang - 1 mRNA ratio was also reduced （ P 〈 0.01 ） in xenografts of NIM group compared with control group. MVD in xenografts of NIM group was significantly lowered down （ P 〈 0.01 ）, CONCLU- SION： NIM down - regulates the expression of Ang- 2 gene and Ang - 2/Ang - 1 mRNA ratio, which may be one of the mechanisms involved in angiogenesis inhibition of COX - 2 inhibitor.