Evodiamine Inhibits The Proliferation Of Human Osteosarcoma By Blocking PI3K/Akt Signaling

Osteosarcoma (OS) is the most common non-hematologic primary malignancy of bone, and multiple chemotherapeutics agents have been applied in treatment of osteosarcoma for over 40 years. Nevertheless, for the unsatisfied prognosis of OS, it is essential to develop a novel treatment strategy. The main emphasis with the problem placed on is not only the anti-proliferation and apoptosis-inducing effect of evodiamine (EVO) on human OS 143B cells, but also the possible mechanisms underlying these effects. The results of our crystal violet staining, flow cytometry, western blotting and in vivo experiment demonstrate that EVO can exhibit a significant proliferation-inhibitory, apoptosis-inducing effect and arrest the cell cycle in 143B cells. According to our data of polymerase chain reaction (PCR), western blotting, and recombinant adenovirus transinfection, we confirmed that EVO can upregulate both protein and gene level of phosphatase and tensin homolog (PTEN) in a concentration-dependent manner in 143B cells. Overexpression of PTEN can reinforce the anti-proliferation effect of EVO in 143B cells, while the knockdown PTEN can upregulate the PI3K/Akt signaling transduction and reverse the proliferation-inhibitory of EVO. The further analysis indicated that EVO can upregulate the expression of PTEN through inactivating PI3K/Akt signaling by decreasing the phosphorylated Aktl/2. From the above results, the conclusion can be reached that PTEN/PI3K/Akt signaling is involved in the proliferation inhibitory effect of EVO in human OS 143B cells.