방사선의학 웹진

바로가기  >

Abstract

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. 

Author information

Jeong YK1,2, Kim MS3, Lee JY2, Kim EH4, Ha H1.

1Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.

2Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.

3Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.

4Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.