Metformin Radiosensitizes P53-Deficient Colorectal Cancer Cells Through Induction of G2/M Arrest and Inhibition of DNA Repair Proteins

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Nov 25

PMID 26599019

Citations 26

Authors

Youn Kyoung Jeong

Mi-Sook Kim

Ji Young Lee

Eun Ho Kim

Hunjoo Ha

Affiliations

Soon will be listed here.

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.

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