Sodium cantharidinate suppresses human osteosarcoma MG‑63 cell proliferation and induces cell cycle arrest by inhibition of PI3K/AKT activation.

Abstract

The function and mechanism of sodium cantharidininate (SC) underlying its suppression of human osteosarcoma (OS) MG‑63 cells were investigated for the first time in the present study. MG‑63 cell proliferation was determined by WST‑1 assay post SC treatment at 0, 12, 24, 48 and 72 h. The results showed that SC effectively inhibited MG‑63 cell proliferation and induced cell cycle arrest at the G0/G1 phase in a dose‑dependent manner. Western blotting revealed that SC induced MG‑63 cell cycle arrest at the G0/G1 phase by means of inhibition of cyclin D1, CDK4 and CDK6 expression. The expression of MAPK and AKT were evaluated using western blotting and FACS experiments to determine whether such signaling pathways are involved in the antiproliferative action of SC on MG‑63 cells. SC significantly inhibited the phosphorylation of AKT, but not mTOR, JNK or P38. PI3K/AKT stimulator, IGF‑1, reversed the SC‑induced cell cycle arrest in the MG‑63 cells. Collectively, our data indicate that the phosphorylation of AKT was inhibited by SC, consequently decreasing the expression of cyclin D1, CDK4 and CDK6 and inducing MG‑63 cell G0/G1 phase arrest. SC has potential as a treatment agent for human osteosarcoma.