Development of a G2/M arrest high-throughput screening method identifies potent radiosensitizers

Translational Oncology

Eunseo Choi¹  Allison DuRoss²  Conroy Sun²  Madeleine Landry²  Dylan Nelson³ 

[1]Corresponding author.

[2]Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR 97201, USA

[3]High-Throughput Screening Services Laboratory, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA

关键词: High-content imaging;    Proflavine hemisulfate;    Cell cycle analysis;    X-ray;    Radiation therapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

Radiation is a powerful tool used to control tumor growth and induce an immune response; however, it is limited by damage to surrounding tissue and adverse effects such skin irritation. Breast cancer patients in particular may endure radiation dermatitis, and potentially lymphedema, after a course of radiotherapy. Radio-sensitizing small molecule drugs may enable lower effective doses of both radiation and chemotherapy to minimize toxicity to healthy tissue. In this study, we identified a novel high-throughput method for screening radiosensitizers by image analysis of nuclear size and cell cycle. In vitro assays were performed on cancer cells lines to assess combined therapeutic and radiation effects. In vivo, radiation in combination with proflavine hemisulfate led to enhanced efficacy demonstrated by improved tumor volume control in mice bearing syngeneic breast tumors. This study provides a proof of concept for utilizing G2/M stall as a predictor of radiosensitization and is the first report of a flavin acting as an X-ray radiation enhancer in a breast cancer mouse model.

【 授权许可】

Unknown