Journal of Radiation Research and Radiation Proces ›› 2016, Vol. 34 ›› Issue (6): 60203-60203.doi: 10.11889/j.1000-3436.2016.rrj.34.060203

• RADIOBIOLOGY AND RADIOMEDICINE • Previous Articles     Next Articles

Effect of LGK-974 in enhancing the radiosensitivity of HepG2 hepatoma cells

TIAN Dan1, WANG Yan1, WANG Qin1, DU Liqing1, XU Chang1, LIU Qiang1, FAN Feiyue2   

  1. 1. Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China;
    2. Institute of Laboratory Animal Sciences, CAMS & PUMC, Beijing 100021, China
  • Received:2016-07-30 Revised:2016-10-08 Online:2016-12-20 Published:2016-12-08
  • Supported by:

    Supported by the National Natural Science Foundation of China (31200634, 31300695), Tianjin science and technology popularization project (15KPXM01SF056), Fundamental Research Funds for CAMS & PUMC (2016ZX310068), and Research Funds for the Inno-vation Team of IRM-CAMS (1605)

Abstract:

To observe the effects of LGK-974 on radiosensitivity of HepG2 cells and explore its possible mechanism, MTT assay was applied to examine the growth inhibition of LGK-974 to HepG2; the radiosensitivity of HepG2 cells treated by 1.0 μmol/L LGK-974 was detected by clone formation assay; the reactive oxygen species level was examined by H2DCFH-DA probe flow cytometry method; the mRNA and protein levels of Nrf2, and the downstream gene HO-1, NQO-1 were accessed by RT-PCR and Western Blot, respectively. The results showed LGK-974 could inhibit HepG2 cells growth, and the IC50 of 24 h, 48 h and 72 h were 4.3 μmol/L, 2.14 μmol/L, and 0.536 μmol/L, respectively (p<0.05); the SERD0 of 1.0 μmol/L LGK-974 was 1.37; LGK-974 could increase the ROS level produced by irradiation (p<0.05); irradiation could increase the transcription and expression of Nrf2, HO-1, and NQO-1, and LGK-974 could weaken these effects. The study reveals that LGK-974 can enhance the radiosensitivity of HepG2 cells. The mechanism might inhibit the Nrf2 signaling pathway and prevent cells reducing the oxidative stress produced by irradiation.

Key words: LGK-974, HepG2 cells, Nrf2, Reactive oxygen species (ROS), Radiosensitization

CLC Number: 

  • R811.5