Lycorine inhibits tumor growth of human osteosarcoma cells by blocking Wnt/β-catenin, ERK1/2/MAPK and PI3K/AKT signaling pathway

Osteosarcoma (OS) is the most common type of primary bone cancer. Even with advances in early diagnosis and aggressive treatment, the overall prognosis for OS remains to be further elevated. Lycorine was an isoquinoline alkaloid mainly existed in the bulb of lyco salvia miltiorrhiza and was shown to inhibit several types of cancer. In the present study, we investigated the anti-OS activity of lycorine and the possible underlying mechanism. We found that lycorine inhibited cell proliferation of human OS cells while had lower cytotoxcity against normal cells, and triggered cell cycle arrest at the G1/S transition. Moreover, we validated that lycorine promoted apoptosis via death receptor pathway and mitochondrial pathway, suppressed migration and invasion by reversing epithelial mesenchymal transition (EMT) and suppressing the degradation of extracellular matrix (ECM) in vitro. In addition, orthotopic implantation model of 143B OS cells further confirmed that lycorine suppressed OS growth and lung metastasis in vivo. Mechanically, lycorine reduced the protein level of β-catenin and its' downstream molecule c-Myc. Furthermore, lycorine also decreased the phosphorylation of ERK1/2 and AKT. Together, our results reveal that lycorine may inhibit tumor growth of OS cells possibly through suppressing Wnt/β-catenin, ERK1/2 and PI3K/AKT signaling pathway.

Keywords: ERK1/2; Lycorine; PI3K/AKT; Wnt/β-catenin; osteosarcoma.