[Abrogation effect of UCN-01 on radiation-induced G2 phase arrest of tumor cells and its mechanism].
OBJECTIVE
Irradiation often causes cell cycle arrest in tumor cells. This study was to observe the abrogation of radiation-induced G(2) phase arrest of p53 mutated human cancer cell lines by 7-hydroxystaurosporine (UCN-01), and explore the mechanism.


METHODS
Human nasopharyngeal carcinoma cell line CNE-1 and human lung adenocarcinoma cell line 973, both with p53 mutation, were used in this study. Human fibroblastoma cell line HT-1080 was used as control. Flow cytometry was used to observe the effects of irradiation on cell cycle of these 3 cell lines, and abrogation effect of UCN-01 on radiation-induced G(2) phase arrest. Western blot was used to detect phosphorylated CDC2-Tyr15 during the abrogation process.


RESULTS
Irradiation resulted in G(2) phase arrest in CNE-1 cells and 973 cells. Proportion of cells in G(2) phase increased from 18.4% to 43.6% in CNE-1 cell line, and from 14.8% to 42.8% in 973 cell line after 2 Gy of irradiation. G(1) phase arrests, measured by "S phase cells consumption", of CNE-1 cells and 973 cells were much lower than that of HT-1080 cells (14.8% and -1.2% vs. 57.0%). Radiation-induced G(2) phase arrests were abrogated by UCN-01 from 63.5% to 16.1% in CNE-1 cell line, and from 35.4% to 16.3% in 973 cell line. UCN-01 suppressed the expression of radiation-induced phosphorylation of CDC2-Tyr15, which was in accordance with the abrogation of radiation-induced G(2) phase delay.


CONCLUSIONS
Main effect of irradiation on cell cycle of p53 mutated CNE-1 cells and 973 cells is G(2) phase arrest. UCN-01 is able to abrogate radiation-induced G(2) phase, which is associated with the reduction of phosphorylated CDC2-Tyr15.
Hui
Zhou-Guang
ZG
Department of Radiation Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100-021, P.R.China.
Li
Ye-Xiong
YX
Yang
Wei-Zhi
WZ
Yu
Zi-Hao
ZH
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D045744:Cell Line, Tumor; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D010315:Particle Accelerators; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase; D019311:Staurosporine