塞来昔布联合奥沙利铂对人肺癌裸鼠移植瘤的治疗作用及其作用机制的研究

目的: 研究COX-2抑制剂与化疗药物奥沙利铂对人肺癌裸鼠移植瘤生长、Survivin表达和微血管生成的影响。 方法: 人肺癌A549细胞接种于裸鼠背部皮下,随机分为四组(对照组;奥沙利铂组;塞来昔布组;奥沙利铂和塞来昔布联合用药组)并给予相应的药物。测量肿瘤体积,42天后处死裸鼠,切取移植瘤组织检测COX-2,VEGF,Sur-vivin表达和微血管密度(MVD)。 结果: 塞来昔布组和奥沙利铂组抑瘤率分别为34.60%和46.70%,奥沙利铂和塞来昔布联合应用组抑瘤率为66.09%。免疫组织化学染色和RT-PCR结果分析显示:奥沙利铂组COX-2,VEGF表达显著高于对照组(P<0.05)。微血管密度与对照组比较无显著性差异(P>0.05)。奥沙利铂组Survivin表达低于对照组,塞来昔布组和联合用药组COX-2,VEGF表达和MVD低于对照组(P<0.05)。 结论: 塞来昔布可抑制人肺癌裸鼠移植瘤的生长、Survivin表达和血管生成。塞来昔布与奥沙利铂联合应用提高了奥沙利铂的抗肿瘤效果。

Effect of Celecoxib Combined with Oxaliplatin on Tumor Growth, Survivin Expression and Angiogenesis in Lung Cancer Xenografts in Nude Mice

Objective: To evaluate the effects of celecoxib combined with oxaliplatin on tumor growth, survivin expression and angiogenesis in lung cancer xenografts in nude mice. Methods: Human lung cancer A549 cells were injected into BALB/c nude mice subcutaneously. The mice were randomly divided into 4 groups: the control group, the Oxaliplatin group, the Celecoxib group and the Celecoxib combined with Oxaliplatin group. On the 42nd day after treatment, tumor tissues were collected and assessed for the detection of COX-2, VEGF, Survivin, and microvessel density (MVD) by immunohistochemistry and RT-PCR. Results: The rate of tumor inhibition was 34.60% in the Celecoxib group, 46.70% in the Oxaliplatin group and 66.09% in the Celecoxib combined with Oxaliplatin group. Immunohistochemical and RT-PCR analysis showed an increase in the expression of COX-2 and VEGF, a decrease in the expression of Survivin in the Oxaliplatin group (compared with the control group, P<0.05), and no obvious differences in MVD (compared with the control group, P>0.05). The expression of COX-2, VEGF, Survivin and MVD was significantly decreased in the Celecoxib group and the Celecoxib combined with Oxaliplatin group. Conclusion: Celecoxib can suppress tumor growth, angiogenesis and expression of Survivin and it can enhance the anti-tumor effect of Oxaliplatin.