Abstract

BACKGROUND AND PURPOSE Osteosarcoma is the commonly seen type of primary malignant bone tumors in children and adolescents. Partial patients with osteosarcoma cannot tolerate the side effects of chemotherapy drugs. Hence, it is urgent to find anti-osteosarcoma drugs with low side effects. Melittin is an anti-tumor Traditional Chinese Medicine with low side effects. The purpose of this study was to explore the anti-osteosarcoma effect of melittin and its possible molecular mechanisms. METHODS The effects of melittin on cell growth were detected by CCK-8, clonal formation and flow cytometry. As well as the related molecules were investigated by Real-time PCR and Western blot. Xenograft model in nude mice was established to observe the effects of melittin on tumor growth and the related molecular expression were detected by immunohistochemistry. RESULTS Melittin can inhibit the proliferation of osteosarcoma 143B cells, reduce colony formation and induce apoptosis, while significantly up-regulate the expression of Bax and Caspase-3, and down-regulate the expression of Bcl-2 proteins. Moreover, treatment with melittin significantly reduced the mRNA and protein levels of β-catenin and Wnt/β-catenin related genes (LRP5, c-Myc, and Survivin) in osteosarcoma 143B cells in vitro. The xenograft model found that melittin significantly inhibited tumor growth and decreased the protein expression levels of β-catenin and Wnt/β-catenin related genes in vivo. CONCLUSION These findings show that melittin could inhibit the growth of osteosarcoma 143B cells, which may be related to the inhibition of Wnt/β-catenin signaling pathway activity, and induce apoptosis by up-regulating the ratio of Bax/Bcl-2 in osteosarcoma 143B cells. Therefore, melittin is a promising anti-tumor drug for treatment of osteosarcoma.