FOXO4 D-retro-inverso peptide increases radiosensitivity of non-small cell lung cancer cells / 中华放射医学与防护杂志

ABSTRACT

Objective To explore the effects of FOXO4 D-retro-inverso peptide (FOXO4-DRI)on the radiosensitivity of non-small cell lung cancer (NSCLC) cells.Methods To detect the effect of FOXO4-DRI on NSCLC cells,H460 and A549 human lung cancer cells were divided into four groups,including untreated control,FOXO4-DRI,γ-ray irradiation and FOXO4-DRI + γ-ray groups.A sigle dose rate of 0.99 Gy γ-rays was used for radiation.H460 cells were administered with 6 μmol/L FOXO4-DRI and A549 cells were adiminstered with 30 μmol/L FOXO4-DRI at 10 min before radiation.Cell viability and survival were detected by CCK-8 assay and colony formation assay,respectively.Cell migration was detected by wound healing assay.Apoptosis and cell cycle arrest were detected with flow cytometry.Results FOXO4-DRI inhibited growth of H460 and A549 cells (t =1.06-50.75,P＜ 0.05),and decreased cell mobility (t =33.37-139.10,P＜0.05) and colony formation (t =5.20-93.48,P＜0.05).FOXO4-DRI also increased apoptosis (t=2.95-42.00,P＜0.05) and caused a cell cycle arrest at G0/G1 phase accompanied with a decreased proportion of G2/M phase (t =3.50-3 1.59,P＜0.05).Furthermore,FOXO4-DRI increased radiosensitivity of both H460 cells and A549 cells (t =2.94-23.40,P＜0.05),caused a Further Decrease of radiation-mediated mobility (t =5.25,7.56,P＜0.05) and colony formation (t =8.43-34.00,P＜ 0.05) and a more increase of radiation-induced apoptosis (t =9.20-11.52,P ＜0.05).FOXO4-DRI also further decreased the proportion of G2/M phase cells but increased the proportion of S phase cells (t =3.85-17.62,P ＜ 0.05).Conclusion FOXO4-DRI increases radiosensitivity of NSCLC cells by inducing apoptosis and suppressing cell proliferation.