低剂量环磷酰胺联合人参皂甙Rg3抑制小鼠肺癌肿瘤血管生成的实验研究

作者	单位
康欣梅	哈尔滨医科大学附属肿瘤医院内科
张清媛	哈尔滨医科大学附属肿瘤医院内科
佟丹丹	哈尔滨医科大学病理学教研室
赵文辉	哈尔滨医科大学附属肿瘤医院内科

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中文摘要:

目的研究持续低剂量环磷酰胺(cyclophosphamide,CTX)联合人参皂甙Rg3对肺癌肿瘤血管生成的影响,观察其抑瘤效果、毒副反应及生存期。方法以荷Lewis肺癌的C57/BL6小鼠为模型,随机分为5组:即低剂量CTX组(简称低CTX组)、最大耐受剂量CTX组(简称高CTX组)、人参皂甙Rg3组、低剂量CTX联合人参皂甙Rg3组(简称联合组)及模型组,治疗中观察肿瘤体积、小鼠体重和外周血白细胞计数及小鼠生存期,测定肿瘤微血管密度(microvasculardensity,MVD)和血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)表达情况。结果低CTX组肿瘤生长比较缓慢,小鼠体重及外周血白细胞数均无明显下降,生存期延长;联合组抑瘤效果更持久而稳定,毒副反应未增加,小鼠生存期更长(P<0.01)。低CTX组较高CTX组MVD下降(P<0.05);与模型组比较,低CTX组和人参皂甙Rg3组MVD及VEGF表达均下降,两者合用时下降更明显(P<0.05)。结论低剂量CTX与人参皂甙Rg3联合应用显示出明显的抗血管生成协同作用,抑瘤效果显著且持久,毒副反应小,生存期较单药治疗延长。

英文摘要:

ObjectiveTo evaluate the anti-angiogenetic effect of the combination of low-dose cyclophosphamide(CTX) and ginsenoside Rg3 in mice with Lewis lung carcinoma, and to observe the anti-tumor effect, toxicity, adverse reaction of the treatment and survival time of the tumor bearing mice. MethodsHolland C57/BL6 Lewis lung carcinoma mice were taken as the model and randomly divided into 5 groups, i.e. the low-dose CTX (LDCTX) group, the maximum tolerable dose CTX (MTDCTX) group, the ginsenoside Rg3 (Rg3) group, the low-dose CTX combined with ginsenoside Rg3 group (LDCTX+Rg3), and the model group. Tumor volume, weight of mice, peripheral white blood cell counts and survival time of mice were observed, tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) gene expression were determined during the therapeutic course. ResultsIn the LDCTX group, tumor grew comparatively slow, no significant decrease in body weight or peripheral white blood cells, and survival time was prolonged. In the LDCTX+Rg3 group, the tumor inhibitory effect was more persistent and steady without any increase of toxicity or adverse reaction. Besides, the survival time of mice was prolonged (<0.01). MVD was lower in the LDCTX group than that in the MTDCTX group (<0.05). Compared with the model group, MVD and VEGF expression were lower in the LDCTX and the Rg3 group, and the lowering action was more significant when the two drugs were used in combination (PWT<0.05). ConclusionThe combination of low-dose CTX and Rg3 has obvious synergetic action of anti-angiogenesis, it shows significant and persistent tumor inhibitory effect, with less toxic and adverse reaction, and could induce longer survival time than treatment of CTX or Rg3 alone.

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