节律化疗对Lewis肺癌血管生成的影响

Antiangiogenic effect of metronomic chemotherapy on lewis lung carcinoma

目的观察环磷酰胺(CTX)节律化疗对Lewis肺癌肿瘤血管生成的影响。方法建立荷Lewis肺癌C57BL/6小鼠模型,随机分为CTX节律化疗组、CTX最大耐受剂量(MTD)组和对照组,于造模后第6天开始分别给予相应治疗。观察小鼠饮食、活动及一般状况,连续测量肿瘤大小和小鼠体质量。处死小鼠后,称瘤重,免疫组织化学方法测定各组肿瘤组织的微血管密度(MVD)及血管内皮生长因子(VEGF)表达情况。结果①与MTD组和对照组相比,节律化疗组肿瘤生长曲线较平缓,动物体质量无下降;②实验结束时,节律组、MTD组和对照组的平均瘤重分别为(1.68±0.37)g、(1.94±0.56)g、(3.75±0.86)g;③节律组、MTD组和对照组的MVD分别为15.09±3.03、23.51±2.78和26.38±2.56,VEGF高表达率分别为46.2%、73.5%和81.3%。结论CTX节律化疗可显著抑制Lewis肺癌的生长及其血管生成,且毒副作用较MTD化疗小。

Objective To observe the effects of metronomic chemotherapy with cyclophosphamide(CTX)on tumor angiogenesis on mouse Lewis lung carcinoma model.Methods Lewis lung carcinoma cells were injected subcutaneously into C57BL/6 mice.C57BL/6 mice were randomised into metronomic group,MTD group and control group.According therapy was given to different groups.The general condition of mice was observed every day.Tumor growth and mice weight were monitored during the experiment.At the 25th day after inoculation,all mice were killed.Tumors were resected,weighed and immunohistochemistry was done.Tumor microvessel density(MVD)and vascular endothelial cell growth factor(VEGF)were detected.Results ①Compared to MTD group and control group,the tumor growth curve in metronomic group was near flat and mice in that group had no weight loss.②At the end of experiment,the weight of tumor in metronomic group,MTD group and control group were(3.75±0.86)g,(1.68±0.37)g,(1.94±0.56)g,respectively.②MVD in metronomic group,MTD group and control group were 15.09±3.03,23.51±2.78,26.38±2.56,respectively.The high expression rate of VEGF were 46.2%,73.5%,81.3%,respectively.Conclusion Metronomic chemotherapy with CTX can inhibit the tumor growth and angiogenesis of Lewis lung carcinoma effectively,and it has lower toxicity than MTD chemotherapy.