Metformin Radiosensitizes p53-Deficient Colorectal Cancer Cells through Induction of G2/M Arrest and Inhibition of DNA Repair Proteins
- 등재 SCIE, SCOPUS
- 발행기관 PUBLIC LIBRARY SCIENCE
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000122847
- 본문언어 영어
- Published As http://dx.doi.org/10.1371/journal.pone.0143596
초록/요약
The present study addressed whether the combination of metformin and ionizing radiation (IR) would show enhanced antitumor effects in radioresistant p53-deficient colorectal cancer cells, focusing on repair pathways for IR-induced DNA damage. Metformin caused a higher reduction in clonogenic survival as well as greater radiosensitization and inhibition of tumor growth of p53(-/-) than of p53(+/+) colorectal cancer cells and xenografts. Metformin combined with IR induced accumulation of tumor cells in the G2/M phase and delayed the repair of IR-induced DNA damage. In addition, this combination significantly decreased levels of p53-related homologous recombination (HR) repair compared with IR alone, especially in p53(-/-) colorectal cancer cells and tumors. In conclusion, metformin enhanced radiosensitivity by inducing G2/M arrest and reducing the expression of DNA repair proteins even in radioresistant HCT116 p53(-/)-colorectal cancer cells and tumors. Our study provides a scientific rationale for the clinical use of metformin as a radiosensitizer in patients with p53-deficient colorectal tumors, which are often resistant to radiotherapy.
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