Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling.

Abstract

Osteosarcoma (OS) is the most common non-hematologic primary malignancy of bone, and multiple chemotherapeutic agents have been applied in the treatment of OS for over 40years. Nevertheless, due to the poor prognosis of OS, it is essential to develop a novel treatment strategy. Evodiamine (EVO), a quinolone alkaloid extracted from the fruit of Evodia rutaecarpa, has been demonstrated to inhibit tumor cell proliferation. Thus, the main aim of the present study was to investigate the anti-proliferative and apoptosis-inducing effects of evodiamine (EVO) on human OS 143Bcells, but also the possible mechanisms underlying these effects. The results of crystal violet staining, flow cytometry, western blot analysis and an invivo experiment demonstrated that EVO exhibits significant inhibitory effects on cell proliferation, exhibits apoptosis-inducing effects and arrests the cell cycle in 143Bcells. According to our findings of polymerase chain reaction (PCR), western blot analysis and recombinant adenoviral transfection, we confirmed that EVO upregulates both the protein and gene levels of phosphatase and tensin homolog (PTEN) in a concentration-dependent manner in 143Bcells. Overexpression of PTEN reinforced the anti-proliferative effect of EVO in the 143Bcells, while knockdown of PTEN upregulated PI3K/Akt signaling transduction and reversed the inhibitory effect of EVO on 143B cell proliferation. Further analysis indicated that EVO upregulated the expression of PTEN by inactivating PI3K/Akt signaling by decreasing phosphorylated Akt1/2. Based on the above results, we conclude that PTEN/PI3K/Akt signaling is involved in the inhibitory effect on human OS 143Bcell proliferation by EVO.