| Objective To observe the effects of LGK-974 on radiosensitivity and explore the possible mechanism on human hepatocellular carcinoma HepG2 cell.Methods MTT assay was applied to examine the growth inhibition of LGK-974 to HepG2;the radiosensitivity of HepG2 cells treated by 1.0μM LGK-974 was detected by clone formationassay;the reactive oxygen species level was examined by H2DCFH-DA probe flow cytometry method;immunofluorescence analysis was performed to detect Nrf2distribution in HepG2 cells;the mRNA and protein levels of Nrf2,and the downstream gene HO-1,NQO-1 were accessed by RT-PCR and western blot,respectively.ResultsThe results showed LGK-974 inhibited HepG2 cells growth,and the IC50 of 24 h,48 h and 72 h were 4.3μM,2.14μM and 0.53μM,respectively(p<0.05);the SERDO of 1.0μM LGK-974 is 1.37;LGK-974 can increase the ROS level produced by irradiation(p<0.05);the Nrf2 of HepG2 cells increased significantly after irradiation,and LGK-974 could inhibit the entry of Nrf2 into the nucleus;irradiation increases the transcription and expression of Nrf2,HO-1,NQO-1,LGK-974 can weaken these effects.ConclusionsThe study reveals that LGK-974 could enhance the radiosensitivity of HepG2 cells.The mechanism might inhibit the Nrf2 signaling pathway and prevent cells reducing the oxidative stress produced by irradiation. |
