Synergistic effects of Endostar combined with β-elemene on malignant ascites in a mouse model

To explore an effective combination therapy for malignant ascites, the therapeutic value of the combination of Endostar, a modified recombinant human endostatin, and β-elemene, an active component of a traditional Chinese herb, in an H22 mouse malignant ascites model was investigated. The optimal dose combination of Endostar and β-elemene was determined by evaluating the inhibition of ascites volume and increase in the survival rate of the mice. Other therapeutic effects and the underlying mechanisms were investigated under the optimal dose combination (8 mg/kg Endostar plus 100 mg/kg β-elemene). The mice were randomly divided into four treatment groups and received intraperitoneal injection once a day for eight days: control (0.9% normal saline), Endostar (8 mg/kg), β-elemene (100 mg/kg) or optimal dose combination (8 mg/kg Endostar plus 100 mg/kg β-elemene), respectively. The results of this study revealed that the combination therapy had significant synergistic effects on the inhibition of ascites formation and a deceased number of tumor cells and protein levels in ascites compared with the results of treatment with a single agent. A decreased peritoneal microvascular permeability and reduction in VEGF, MMP-2 and hypoxia inducible factor 1α (HIF1α) was noted in the combination group, when compared with single agent treatment. These studies found that in the ascitic tumor cells, the protein levels of VEGF and MMP-2, as well as levels of VEGF mRNA, were significantly inhibited by the combination therapy. The potentiating effects of the combination of Endostar with β-elemene suggest that this novel therapy may yield an effective therapy for the treatment of malignant ascites.