Inhibitory effects of melittin on osteosarcoma xenografts in nude mice and its action on vasculogenic mimicry / 肿瘤

ABSTRACT

Objective: To investigate the antitumor effects of melittin on UMR-106 cells with osteosarcoma xenografts in nude mice and its action on vasculogenic mimicry (VM) in vitro and in vivo. Methods: A three-dimensional cell culture system was formed on matrigel coats in vitro. Inhibitory action of melittin on the VM of UMR-106 cells was observed in vitro. Osteosarcoma was orthotopically transplanted in nude mice. The mice were randomly divided into three groups: normal saline (NS)-treated group, melittin group (320 μg/kg) and DDP-treated group(2 mg/kg). The drug was administered intratumorally for 10 d. The tumor volume and weight inhibition ratio were calculated, respectively. The VM density in tumor tissues was detected by CD34 and PAS double staining in vivo. The expressions of hypoxia-inducible factor-1α(HIF-1α) and matrix metalloproteinase-2 (MMP-2) proteins were determined by immunohistochemical staining and Western blot. Results: Melittin broke down the mesh and round architectonic of VM in osteosarcoma in vitro. The tumor weight inhibition ratio was 38.92% and the volume inhibition ratio was 43.04%. The VM density and the expressions of HIF-1α and MMP-2 proteins were decreased in the melittin group than that in the NS-treated group (P <0.01). Conclusion: Melittin markedly inhibites the growth of osteosarcoma UMR-106 xenografts in nude mice. The mechanism may be due to down-regulation of HIF-1α and MMP-2 expression and the inhibition of VM.