Altered expression of a metformin-mediated radiation response in SA-NH and FSa tumor cells treated under in vitro and in vivo growth conditions. (3rd July 2017)

• Record Type: Journal Article
• Authors: Murley, Jeffrey S.; Miller, Richard C.; Senlik, Raziye Rana; Rademaker, Alfred W.; Grdina, David J.
• Is Part Of: International journal of radiation biology. Volume 93:Number 7(2017:Jul.)
• Page Start: 665
• Page End: 675
• Publication Date: 2017-07-03
• Subjects: Metformin -- p53 -- N-acetyl-l-cysteine -- emodin -- rotenone; Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.1080/09553002.2017.1304592
• Languages: English
• ISSNs: 0955-3002

Abstract

Abstract: Purpose: To assess the radiosensitizing effect of the biguanide drug metformin used alone or in combination with reactive oxygen species (ROS) modifying agents N -acetyl-L-cysteine (NAC) or emodin, and contrasted to the mitochondrial complex 1 inhibitor rotenone in altering the radiation responses of the p53 wild-type SA-NH and p53 mutant FSa mouse tumor lines grown either in vitro or in vivo. Materials and methods: Tumor cells were grown to confluence in vitro and exposed to a single 4 Gy dose in the presence or absence of metformin (5 mM) and ROS modifiers or to 10 Gy with or without metformin as tumors in the flanks of C3H mice using a tumor growth delay assay. Results: Both metformin and rotenone protected SA-NH ( p < .001) while sensitizing FSa ( p < .001) to 4 Gy. Neither NAC nor emodin altered metformin's action. Metformin was also directly toxic to FSa cells ( p = .002). In contrast, in vivo metformin (250 mg/kg) sensitized both SA-NH (9-day growth delay, p < .05) and FSa (4-day growth delay, p < .05) tumors if administered 1 h before irradiation. Conclusion: Metformin effects on tumor cells measured under in vitro conditions may differ from those determined in vivo due to p53 and heterogeneous environmental factors.