联合低剂量化疗对小鼠Lewis肺癌抗血管生成和抗肿瘤作用的研究  

Combined Low-dose Chemotherapy Inhibiting Angiogenesis and Growth of Lewis Lung Cancinoma Xenografts in Mice

作　　者：邱萌[1] 易成[1] 侯梅[1] 

机构地区：[1]四川大学华西医院肿瘤化疗科,成都610041

出　　处：《四川大学学报（医学版）》2006年第4期534-537,共4页Journal of Sichuan University(Medical Sciences)

基　　金：教育部留学回国人员基金(2001345);四川省科技基金重点项目(015G046-06)资助

摘　　要：目的观察低剂量环磷酰胺(CTX)、紫杉醇(PTX)联合化疗的抗血管生成作用、抑瘤作用及毒副反应。方法建立小鼠L ew is肺癌模型,将40只C 57BL/6小鼠随机分为四组:生理盐水对照组、CTX单药组(170 m g/kg,q6d)、PTX单药组(10 m g/kg,q7d)、CTX+PTX联合治疗组。分别测定小鼠肿瘤体积、平均瘤重、抑瘤率,免疫组化法检测微血管密度(M VD),免疫组化图像分析法半定量检测血管内皮生长因子(VEGF)的表达。结果低剂量CTX+PTX联合治疗组的肿瘤体积、平均瘤重低于各单药治疗组(P<0.005),抑瘤率高于各单药治疗组(P<0.005);联合治疗组肿瘤组织M VD数和VEGF表达均低于各单药治疗组(P<0.005)。紫杉醇单药治疗组毒副反应最小,其他各治疗组毒副反应无差异,可耐受。结论低剂量CTX、PTX两药联合治疗比单药治疗具有更强的抑制血管生成及抑制肿瘤生长作用,毒副作用可被耐受。Objective To investigate the antiangiogenic and antitumor effects of combined low-dose cyclophosphamide（CTX） and paclitaxel （PTX）. Methods In this experiment, Lewis lung carcinoma model was established in C57BIL6 mice. Forty mice were randomly divided into four groups： control group, cyclophosphamide （170 mg/kg, q6d） group, paclitaxel （10 mg/kg, q7d） group, and cyclophosphamide plus paclitaxel group. The growth of tumor and the sideeffect of each therapy were investigated. Microvessel density （MVD） was assessed by CD31 immunostaining, and immunohistochemistry （IHC） image analysis was performed for semiquantification of vascular enthothelial growth factor （VEGF）. Results The combined low-dose therapy with cyclophosphamide and paclitaxel was most effective for antagonizing tumor-associated angiogensis; the mice of this group had the lowest MVD and VEGF expression, compared to mice of other groups （P 〈 0.005）. The combination therapy also brought about higher antitumor rate, lower tumor volume, and lower tumor weight than did the single therapy （P 〈 0.005）. Paclitaxel （10 mg/kg, q7d） therapy had the slightest side-effects; other therapies had similar acceptable side effects. Conclusion The combined use of low dose cyclophosphamide and paclitaxel has synergistic antiangiogenic effect on the mouse model of Lewis lung carcinoma; the combination of these two agents is clearly more effective for inhibiting angiogenesis and growth of tumor.

关 键 词：低剂量 化疗 环磷酰胺 紫杉醇 抗血管生成 

分 类 号：R734.2[医药卫生—肿瘤]