[Abrogation of radiation-induced G2 arrest and radiosensitization by 7-hydroxystaurosporine (UCN-01) in human nasopharyngeal carcinoma cell line].
OBJECTIVE
To enhance the radiosensitivity of cancer cell is one of the most important way to improve the effect of radiotherapy. This study was designed 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 effect of irradiation and UCN-01 on cell cycle of human nasopharyngeal carcinoma cells (CNE-1) with mutated p53. The effect on 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 at G2 phase, comparing to the control group (18.4%), was increased to 43.6%, 77.4% and 86.4% after 12 hours with 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 from 63.5% in the control group to 28.5%, 25.0%, 16.1% and 13.7%, respectively. UCN-01 resulted in a radiosensitization in CNE-1 cells. The SERs were 2.60 and 3.09, for 100 nmol/L and 200 nmol/L of UCN-01, respectively.


CONCLUSIONS
Radiosensitization of UCN-01 in CNE-1 cells characterized by mutated p53 is associated with its abrogation of radiation-induced G2 arrest.
Hui
Zhou-Guang
ZG
Department of Radiation Oncology, Cancer Hospital (Institute), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, P. R. China.
Li
Ye-Xiong
YX
Yang
Wei-Zhi
WZ
Wu
Jun-Xin
JX
Yu
Zi-Hao
ZH
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine