希罗达对4T1乳腺癌小鼠肿瘤血管生成的影响

目的:探讨不同剂量希罗达对4T1乳腺癌小鼠肿瘤血管生成的影响,并观察其抑瘤效果和毒副作用。方法:建立荷4T1乳腺癌小鼠模型,分别给予持续低剂量希罗达、最大耐受剂量(maximumtolerateddose,MTD)希罗达、低剂量希罗达治疗,观察肿瘤体积、小鼠体重和外周血白细胞计数及小鼠生存期。实验终末时行免疫组化染色,测定肿瘤微血管密度(MVD)和血管内皮生长因子(VEGF)表达情况。结果:与对照组和MTD希罗达治疗组比较,持续低剂量希罗达治疗组小鼠肿瘤MVD值和VEGF表达均显著降低(P<0.05)。与MTD希罗达治疗组比较,持续低剂量希罗达治疗组肿瘤生长比较缓慢,并且没有明显的体重减轻或白细胞数下降等毒性迹象,小鼠生存期无显著延长(P>0.05)。结论:持续低剂量希罗达给药方式靶向于乳腺癌血管生成,不易产生耐药,增加了抑瘤效果,毒副作用小,动物生存质量明显提高。

Antiangiogenic Effect of Xeloda on 4T1 Mammary Cancer

Objective:To evaluate the the antiangiogenic effect of Xeloda on the mice with 4T1 mammary carcinoma,and to observe its antitumor effect,toxicity and side effects.Methods:80 BALB/c mice modd with 4T1 mammary carcinoma was es- tablished and randomized into four groups:control group,continuous low dose of Xeloda group,maximum tolerated(MTD)dose of Xeloda group,and low dose of Xeloda therapy group.Then size of tumor,weight of the mice,peripheral white blood cell counts and survival period of the mice in each group were observed.At the end of the experiment,tumors were given immunohistochemi- cal staining.Tumor microvascular density(MVD)and VEGF expression were detected.Results:Compared with control group and MTD Xeloda therapeutic group,MVD and VEGF expression decreased in continuous low dose of Xeloda therapeutic group (P<0.05),in which,tumors grew slowly,without apparent body weight loss or leucopenia.Conclusion:The continuous low dose of Xeloda increases the efficacy of targeting the tumor microvasculature,and produces therapeutic activity with less toxicity and im- proves animal survival quality.This experiment suggests a new safe therapy for controlling advanced breast cancer,which is expect- ed to improve quality of patient's life and relieve their suffering.