Potentiation of radiosensitivity by staurosporine associated with abrogation of G2 phase arrest / 药学学报

ABSTRACT

<p><b>AIM</b>To investigate the radiosensitizing effect and mechanism of action of staurosporine (STP) in human colon carcinoma HT-29 and breast cancer MCF-7/ADR cells.</p><p><b>METHODS</b>The effect of STP on the cytotoxicity of X-ray was determined by clonogenic assay. The effect of STP on cell cycle arrest induced by X irradiation was studied in two cell lines by using flow cytometry, Western Blotting was performed to indicate the changes of cyclin B1 and cdc2 protein levels.</p><p><b>RESULTS</b>STP sensitized the two cell lines to X-ray by clonogenic assay. STP potentiated the cytotoxicity of X-ray by 2.10- and 2.09-fold in HT-29 and MCF-7/ADR cells. Flow cytometry assay showed that exposure of HT-29 and MCF-7/ADR cells to X-ray caused cells arrest in G2 phase. The percentage of arrest G2 phase cells were 56% and 52.7%, respectively. The addition of STP after irradiation resulted in a dose-dependent reduction of G2 phase arrest induced by X-ray. Furthermore, the results showed that STP blocked decrease of cyclin B1 expression induced by X-ray, while mitotic index measurement indicated that X-ray-irradiated cells treated with STP entered mitosis. The data suggested that the potentiation of cytotoxicity of X-ray by STP is associated with the suppression of cyclin B1 expression, which result in the abrogation of G2 arrest, before the cells entered into M phase, they had not enough time to repair.</p><p><b>CONCLUSION</b>STP is a potent G2 checkpoint abrogator and markedly enhanced the cytotoxicity of X irradiation in the p53 mutant cancer cells.</p>