CTX小剂量化疗在抗肺癌血管生成中的作用  

The effect of low-dose cyclophosphamide chemotherapy on angiogenesis of lung carcinoma

作　　者：厉明[1] 梅同华[1] 张明川[1] 李长毅[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010

出　　处：《肿瘤》2007年第7期523-526,共4页Tumor

基　　金：重庆市卫生局资助项目(编号:200453)

摘　　要：目的:研究小剂量环磷酰胺(CTX)对肺癌血管生成的影响及其机制。方法:培养人肺腺癌A549细胞,建立裸鼠移植瘤模型,随机分为小剂量CTX组、大剂量CTX组和对照组进行化疗,观察裸鼠体重变化和抑瘤效果,免疫组化检测肿瘤微血管密度(MVD)、缺氧诱导因子-1α(hypoxia-inducible factor1 alpha,HIF-1α)和VEGF的表达。结果:小剂量组肿瘤生长缓慢,体重减轻等副作用明显小于大剂量组和对照组(P<0.01或P<0.05);与大剂量组、对照组比较,小剂量组MVD、HIF-1α和VEGF表达均明显减少(P<0.01),且小剂量组移植瘤中HIF-1α和VEGF、HIF-1α和MVD、VEGF和MVD之间均有相关性。结论:与大剂量组和对照组相比,小剂量CTX化疗组能更显著地抑制肺癌血管生成,抑瘤效果更明显,其机制可能与下调HIF-1α蛋白表达有关。Objective：To study the efficacy of continuous low-dose cyclophosphamide （CTX） chemotherapy on the angiogenesis of lung carcinoma and the corresponding mechanism. Methods：Cultured A549 lung adenocarcinoma cells were transplanted into BALB/c nude mice. Three groups were randomly divided： low-dose CTX group, high-dose CTX group, and control group. The body weight of nude mice and the tumor growth were recorded. Tumor microvessel density （MVD） and the expression of vascular endothelial growth factor （VEGF） and hypoxia-inducible factor 1 alpha （HIF-1α） were detected by immunohistochemical staining. Results：The tumor growth was delayed and the side effects such as body weight loss was significantly relieved in low-dose CTX group compared with highdose CTX group and control group（ P 〈 0.05 or P 〈 0.01 ）. The level of MVD and expression of HIF-1α and VEGF were significantly decreased in low-dose CTX group than those in high-dose CTX group and control group （P 〈0.01 ）. HIF-1α had significant correlation with VEGF and MVD（ P 〈 0.05 ） and MVD was significantly associated with VEGF expression in low-dose CTX group（ P 〈 0.05 ）. Conclusion：Compared with high-dose CTX chemotherapy and normal saline therapy, the continuous low-dose CTX chemotherapy has higher efficacy in inhibiting the tumor growth and angiogenesis. The mechanism may be due to the down-regulation of HIF-1α expression.

关 键 词：肺肿瘤 新生血管化 病理性 缺氧诱导因子1 Α亚基 血管内皮生长因子类 

分 类 号：R734.2[医药卫生—肿瘤]