节律化疗联合最大耐受剂量化疗抗肿瘤作用实验探究.docVIP

节律化疗联合最大耐受剂量化疗抗肿瘤作用实验探究 　【摘要】 目的 探讨环磷酰胺（CTX）节律化疗联合最大耐受量（MTD）化疗对小鼠Lewis肺癌(LLC)肿瘤生长、血管生成和远处转移的影响。方法 荷瘤小鼠随机分4组：分别为（1）CTX节律化疗组；（2）MTD组；（3）联合组（CTX节律化疗联合MTD化疗）；（4）对照组。观察各组肿瘤生长及肺转移情况，检测小鼠肿瘤组织和肺组织中CD34、基质金属蛋白酶-9（MMP-9）和趋化因子受体-4(CXCR4)蛋白的表达。结果 CTX节律化疗联合MTD化疗对小鼠LLC的肿瘤生长、血管生成和远处转移均有显著的抑制作用。联合组和节律组的微血管密度(MVD)、肺转移率、MMP-9和CXCR4蛋白的表达明显低于对照组和MTD组 (Plt;0.05)。结论 在MTD化疗的基础上联合节律化疗可明显抑制LLC的肿瘤生长、血管生成和远处转移。节律化疗有可能通过下调瘤组织中MMP-9和CXCR4蛋白的表达而发挥作用。 【关键词】 节律化疗 环磷酰胺 血管生成 基质金属蛋白酶-9 趋化因子受体-4　 【Abstract】 Objective To detect the effect of cyclophosphamide（CTX） administered by means of metronomic chemotherapy combined maximum tolerated dose （MTD） chemotherapy on the angiogenesis, carcinogenesis and metastasis of Lewis lung cancer(LLC) on C57BL/6 mouse model. Method The mice were randomly divided into four groups:（1）metronomic chemotherapy group,（2）MTD group,（3）combination group（metronomic chemotherapy combined MTD group）,（4）control group. Tried to deserve the tumor growth and lung metastasis of every group and detect the expression of CD34, MMP-9 and CXCR4 in tumor tissue and lung. Results CTX administered by metronomic chemotherapy combined with MTD inhibited significantly tumor growth, angiogenesis and metastasis of LLC. The MVD, lung metastasis rate, expression of MMP-9 and CXCR4 of combination group and metronomic group were much lower than control group and MTD group (Plt;0.05). Conclusion Based on MTD chemotherapy, CTX administered by concurrent metronomic chemotherapy, appears to inhibit significantly tumor growth, angiogenesis and metastasis of LLC. Potentially, by means of down regulating the expression of MMP-9, and CXCR4 in tumor tissue, metronomic chemotherapy performs. 【Key words】 metronomic chemotherapy; cyclophosphamide（CTX）; angiogenesis; matrix metalloproteinase-9（MMP-9）; chemokine receptor-4（CXCR4） 近年来发现低剂量、高频度的节律化疗对肿瘤血管内皮细胞及其前体细胞具有破坏作用而表现出极好的抗血管生成作用。在我们以前的实验中，发现环磷酰胺（CTX）最大耐受量（MTD）化疗对小鼠Lewis肺癌的生长抑制作用优于节律化疗，而节律化疗的不良反应轻且有明显的抗血管生成作用。据此推测如果把节律化疗联合MTD化疗有可能会进一步提高疗效。本报告研究了联合两种用药方法对肿瘤的抑