Cox-2抑制剂联合顺铂治疗肺癌血管生成的研究进展

Huiyan Wei, Qing Zhang
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摘要

目的探讨选择性环氧化酶-2 (COX-2)抑制剂尼美舒利(NIM)及联合顺铂(DDP)对裸鼠移植瘤A549细胞血管生成的影响及其体内治疗恶性肿瘤的机制。方法建立肺癌A549细胞和A549裸鼠肺异种移植模型。按照随机数字表法将受试者分为4组进行药物干预:对照组、NIM组、DDP组、NIM+ DDP组,每组8人,观察一般情况。第22天颈椎脱位处死小鼠,取肿瘤组织,称重,测量肿瘤直径,计算肿瘤抑制率。为了明确尼美舒利单用或联合顺铂对A549肺癌异种移植肿瘤新生血管的影响,用CD31标记微血管,用微血管计数计算微血管密度。采用免疫组化方法检测肺癌A549裸鼠血管内皮生长因子的表达。结果本研究成功构建了肺癌A549裸鼠模型。NIM+ DDP组肿瘤体积在第9天、第13天、第17天、第21天的增大速度较其他3组慢(P<0.001)。Nim+ DDP组肿瘤抑制率最大。NIM+ DDP组微血管密度低于其他3组(F=27.861, P<0.001)。结论选择性COX-2抑制剂可抑制血管生成,提示选择性COX-2抑制剂具有抗肿瘤能力,可作为肺癌的靶向治疗药物。选择性COX-2抑制剂联合顺铂对肺癌A549细胞裸鼠新生血管因子表达及移植瘤生长的抑制作用更为显著。关键词:肺肿瘤;血管内皮生长因子;环氧化酶-2的抑制作用
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Cox-2 inhibitors in combination with cisplatin for lung cancer research progress of angiogenesis
Objective To investigate the selective cyclooxygenase-2 (COX-2) inhibitor nimesulide (NIM) and in combination with cisplatin (DDP) on A549 cells in nude mice transplanted tumor angiogenesis and its mechanism for the treatment oflung cancer in vivo. Methods Lung cancer A549 cells and established A549 lung xenografts in nude mice model.According to the method of random number table, the subjects were divided into four groups for drug intervention: control group, NIM group, DDP group, NIM+ DDP group, each group of 8, and the general state was observed.Mice were killed by cervical dislocation on 22nd days, then obtained tumor tissues, weighed tumor, measured tumor diameter and calculated tumor inhibition rate.To clarify the influence of nimesulide alone or in combination with cisplatin in A549 lung cancer xenograft tumor neovascularization, labeled microvessel with CD31 and counted microvessel density using microvessel counts.Immunohistochemistry was used to detect the expression of endovascular endothelial growth factor in lung cancer A549 in nude mice. Results In this study, a nude mouse model of lung cancer A549 was successfully constructed.The tumor volume of NIM+ DDP group increased more slowly than the other three groups on the 9th, 13th, 17th and 21st day (all P<0.001). Nim+ DDP group had the largest tumor inhibition rate.The microvessel density of NIM+ DDP group was lower than that of the other three groups (F=27.861, P<0.001). Conclusions The selective COX-2 inhibitors could inhibit angiogenesis, suggesting that selective COX-2 inhibitors have anti-tumor capabilities and may be used as a lung cancer targeted therapy.The selective COX-2 inhibitor combined with cisplatin had a more significant inhibitory effect on the expression of neovascularization factors and the growth of transplanted tumor in nude mice with lung cancer A549 cells. Key words: Lung neoplasms; Vascular endothelial growth factors; Inhibition of cyclooxygenase-2
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