Correlation of PI3K / Akt signaling pathway with anti-proliferative effect of evodiamine in colon cancer cells

Objective To determine the anti-proliferative effect of evodiamine( Evo) on colon cancer cells and investigate the possible underlying mechanism. Methods Lo Vo cells were treated with 0,0. 5,1,2and 4 μmol / L Evo,and then the anti-proliferation effect of Evo was assessed by crystal violet staining. Flow cytometry was used to determine the apoptosis of Lo Vo cells after the treatment of 0,0. 5,1 and 2 μmol / L Evo.Western blotting was adopted to detect the expression of proliferating cell nuclear antigen( PCNA) and Caspase-3 in the cells treated with 0,0. 5 and 1 μmol / L Evo. Hypoxia inducible factor 1-alpha( HIF-α)-responsive firefly luciferase reporter was employed to measure the transcription activity of HIF-1α in 0,0. 5,1 and 2 μmol / L Evo treated cells,and Western blotting was used to detect the expression of HIF-1α,Akt1 /2,and p-Akt1 /2in the Lo Vo cells. Results Evo obviously inhibited the proliferation of Lo Vo cells,down-regulated the expression of PCNA and promoted the cell apoptosis. Luciferase reporter system indicated that Evo decreased the transcriptional activity of HIF-1α in a dose-dependent manner( Evo 0. 5 μmol / L,P < 0. 05; 1 or 2 μmol / L,P < 0. 01). Western blotting showed that the expression levels of HIF-1 α and p-Akt1 /2 were reduced after Evo treatment. Conclusion Evo inhibits the proliferation and promotes the apoptosis in Lo Vo cells,which may be due to its down-regulating HIF-1α and inhibiting the transconduction of PI3 K / Akt signaling pathway.