biostudies-literatureGonnissen ACancer Research UKMedical Research CouncilE399https://www.ebi.ac.uk/biostudies/studies/S-EPMC5343511biostudies-literatureUnknown18(2)The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1). The effect on proliferation, radiosensitivity, apoptosis, cell cycle distribution, reactive oxygen species production, DNA repair, gene and protein expression was investigated. FurthermoInternational journal of molecular sciencesThe Effect of Metformin and GANT61 Combinations on the Radiosensitivity of Prostate Cancer Cells.PMC5343511MC_PC_1202020407Isebaert SGonnissen AMuschel RJMcKee CMHaustermans KfalseThe Effect of Metformin and GANT61 Combinations on the Radiosensitivity of Prostate Cancer Cells.The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1). The effect on proliferation, radiosensitivity, apoptosis, cell cycle distribution, reactive oxygen species production, DNA repair, gene and protein expression was investigated. Furthermo2017-01-01T00:00:00Z2017 Feb2025-04-04T14:32:44.791Z2019-03-27T02:38:16ZS-EPMC53435112820883810.3390/ijms18020399