Objective To explore the effect of wortmannin (WM),an inhibitor of PI3K signalingpathway,on the radiation sensitivity of human malignant glioma cells (U251) and the underlyingmechanism.Methods U251 cells were pretreated with 10 μmol/L WM for 2 h and irradiated with 10 GyX-rays,then the activity of PI3K/Akt signaling pathway,the colony-forming ability and apoptosis weredetected to evaluate the effect of WM on radiosensitivity.The protein expressions of cleaved Caspase-3,Bax,Bcl-2 and XIAP were detected with Western blot assay.Results The expression of phospho-Akt wassignificantly inhibited by the pretreatment of cells with 10 μ mol/L WM (t =0.000 1,P ＜0.01).The ratioof apoptotic cells in the WM + IR group was significantly increased from (2.14 ± 1.32)％ of control groupand (11.5 ±2.9)％ of IR group to (22.6 ±3.8)％ (t =0.009 3,0.002 7,P＜0.01).The colony-forming rate of WM + IR group was decreased from (88.54 ± 4.76) ％ of control group and (56.31 ±4.05)％ of IR group to (12.25 ±9.59)％ significantly (t=0.000 03,0.000 2,P＜0.01) accompaniedwith the increases of Caspase-3 and Bax/Bcl-2 but decrease of XIAP.Conclusions WM significantlyincreased the radiation sensitivity of human malignant glioma cells by inhibiting the activity of PI3Ksignaling pathway and the expressions of Bcl-2 and XIAP and activating Caspase-3 and Bax.