【Objective】 To explore the possibility that a AKT inhibitor-124005 enhance radiosensitivity and its potential mechanism. 【Methods】 CCK8 assay was conducted to determine the IC50 value of 124005 in CNE1 cell. The radiosensitizing effect of 124005 in CNE1 and the effect of 3-MA on survival curve after radiation were detected by cell colony assay. The DNA damage of CNE1 cell was examined by detection of histone variant H2AX(γ-H2AX) foci. GFP-LC3 was transinfected into the cells to detect autophagy measuring by confocal microscopy. Flow cytometry with Annexin V-PI staining was used to assess the apoptosis and cell cycle arrest. The expression of related proteins such as p-Akt

p-GSK-3

p-PRAS40

cleaved Caspase-3

cleaved PARP

LC3-Ⅱ

and Beclin 1 were detected by Western blot analysis.【Results】 The IC50 value of 124005 in CNE1 was 30.5 μmol/L. Colony assay showed that the DEF of radiation+ continuous 8 μmol/L 124005 was 1.92 and that of radiation+72h 12.5μmol/L 124005 was 1.12 respectively in CNE1 cell. Twenty-four hours after radiation

γ-H2AX focus disappeared in radiation alone group

but the accumulation of γ-H2AX focus was observed in 124005+radiation group. Twenty-four hours after treatment of radiation+20 μmol/L 124005

ring-shaped structures were detected in the cytosol of CNE1 cell tranfected by GFP-LC3 by confocal microscopy. Annexin V staining showed that 124005 significantly enhance apoptosis of CNE1 after radiation

the ratio reached 52.9%. Western blot showed that 124005 significantly down-regulated the expression of p-AKT

p-GSK-3 and p-PRAS40 and up-regulated the expression of cleaved caspase-3

cleaved PARP

Beclin 1 and LC3-Ⅱin CNE1 after radiation. 3 mmol/L 3-MA significantly inhibited the expression of LC3-Ⅱwhen combined with 124005 + radiation. Colony formation assay indicated that 3-MA significantly reduced cell death induced by radiation+124005. The value of DEF was lower in 3-MA absence group (1.69 VS 1.97).【Conclusion】 124005 inhibit the expression of AKT and its downstream pathway. It radiosensitize CNE1 cells by delaying DNA damage repair and inducing apoptosis and autophagy cell death. It deserves further investigation as a potential radiosensitizing strategy.