Objective      To study the role of evodiamine (EVO) in inducing apoptosis of small-cell lung cancer H1688 and H446 cells by inhibiting PI3K/AKT pathway.       Methods      H1688 and H446 cells were treated with EVO at different concentrations (1

5

20 μmol/L) for different time periods (3

6

12

24 and 48 h)

respectively. Thereafter

p-AKT was assayed by Western blotting. After pretreatment with PI3K/AKT pathway activator IGF-1 or inhibitor LY294002

H1688 and H446 cells were treated with EVO. Subsequently

p-AKT was detected by Western blotting. After H1688 cells were pretreated with IGF-1 and then treated with EVO

they were stained with Annexin-V/PI

and analyzed by flow cytometry. The expression of Bcl-2

Bax and Caspase-3 was detected by Western blotting respectively. After H1688 cells were treated with different concentrations of EVO

the expression levels of PTEN and t-AKT were assayed byWestern blotting

and AKT mRNA level was detected by RT-PCR.       Results      Compared with the control group

p-AKT expression was decreased in H1688 and H446 cells treated with different concentrations of EVO for different times(P0.05). In addition

IGF-1 attenuated down-regulation of p-AKT in H1688 and H446 cells induced by EVO (P0.05)

and inhibited the apoptosis of H1688 cells induced by EVO. There was no significant difference between EVO and LY294002 in the effect of down-regulating p-AKT (P0.05). EVO showed no significant effect on the expression of t-AKT protein and AKT mRNA (P0.05).However

EVO significantly increased the expression of PTEN protein(P0.05).       Conclusion      Inhibition of PI3K/AKT pathway plays a key role in EVO-induced apoptosis of small-cell lung cancer H1688 and H446 cells.