[Experimental study on anti-angiogenesis in mice with Lewis lung carcinoma by low-dose of cyclophosphamide combined with ginsenoside Rg3].

OBJECTIVE: To 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.
METHODS: Holland 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.
RESULTS: In 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 (P < 0.01). MVD was lower in the LDCTX group than that in the MTDCTX group (P< 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 (P < 0.05).
CONCLUSION: The 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.