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 G 2 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 G 2 arrest in a dose dependent manner. The proportion of cells in G 2 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 G 2 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 G 2 phase of 35.4% in the control group to 23.5%, 19.6%, 16.3% and 12.4%, respectively. UCN 01 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 G 2 arrest.