FOXO4 D-retro-inverso peptide increases radiosensitivity of non-small cell lung cancer cells

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=3.50-31.59, 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. Key words: Cell apoptosis; Radiosensitivity; FOXO4-DRI; Lung cancer; Cell proliferation