Objective: To investigate the radiosensitization by pentoxifylline (PTX) in human hepatoma cell line HepG2 and its possible mechanism.
Methods: MTT assay was used to evaluate the cytotoxicity of PTX and clonogenic assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). Flow cytometry was performed to observe the changes in the cell cycle of HepG2 cells in response to X-ray irradiation and the effect of PTX intervention.
Results: The cytotoxicity of PTX increased in a dose-dependent manner following a 24-hour treatment, with the optimal dose range of 1-5 mmol/L. A sub-toxic dose of PTX at 2 mmol/L was used in the subsequent experiments. PTX significantly reduced the clonogenic activity and enhanced the radiosensitivity of HepG2 cells with a SER of 1.3+/-0.16 at the dose of 2 mmol/L. Irradiation resulted in cell cycle arrest at G2 phase in HepG2 cells, and the percentages of HepG2 cells in G2-M phase were 32.15% and 19.52% respectively after exposure to 6 Gy radiation alone and to 6 Gy plus 2 mmol/L PTX at 20 h, demonstrating the effectiveness of PTX in resolving radiation-induced G2 arrest.
Conclusion: Radiosensitization by PTX is possibly associated with the abrogation of G2 arrest in HepG2 cells following radiation exposure.