Potentiation of radiosensitivity by 7-hydroxystaurosporine (UCN-01) in a pulmonary adenocarcinoma cell line

Objective: To investigate the radiosensitization of 7-hydroxystaurosporine (UCN-01) by its abrogation of radiation-induced G2 arrest. Methods: Flow cytometry was used to observe the cell-cycle effect of X-ray irradiation and UCN-01 on human pulmonary adenocarcinoma cells (973) with mutated p53. The effect of radiosensitivity was determined by clonogenic assay and was quantified by calculating the sensitive enhancement ratio (SER). Results: Irradiation resulted in G2 arrest in a dose-dependent manner. The proportion of cells in G2 phase increased from 14.8% in the control group to 42.8%, 55.9% and 60.5% 12-hour after irradiation of 2, 4 and 6 Gy respectively. Radiation-induced G2 arrest was abrogated by UCN-01 in a concentration-dependent manner. UCN-01 at the concentrations of 50, 100, 200 and 400 nmol/L decreased the proportion of cells in G2 phase of 35.4% in the control group to 23.5%, 19. 6 % , 16. 3 % and 12. 4 % , respectively. UCN201 resulted in a radiosensitization in 973 cells. SER was 1.13 and 1.31 respectively for 200 nmol/L and 400 nmol/L UCN-01. Conclusion: Radiosensitization of UCN-01 in 973 cells characterized by mutated p53 is associated with its abrogation of radiation-induced G2 arrest