[The role of cell cycle arrest in radiosensitization of nasopharyngeal carcinoma cell line CNE1 by inhibiting ATM expression].
OBJECTIVE
Cell cycle regulation is one of the most important determinants to ionizing radiosensitivity of cells. ATM gene is closely related with DNA damage repair and cell cycle checkpoints control. We previously reported that suppressing ATM expression with antisense ATM RNA could enhance radiosensitivity of nasopharyngeal carcinoma (NPC) cell line CNE1. This study was to explore the involved changes of cell cycle and the mechanisms of cell cycle arrest.


METHODS
ATM gene was constructed into retrovirus vector pDOR to form recombinant pDOR-atm. CNE1 cells were transfected with pDOR-atm (CNE1/pDOR-atm cells) or pDOR (CNE1/pDOR cells) and irradiated with X-ray. Cell cycle and cell apoptosis were detected by flow cytometry at different time points after irradiation.


RESULTS
S phase arrest was detected at 1, 4, and 8 h after irradiation in both groups, and G2 arrest at 24, and 48 h, while no comparable G1 arrest and apoptosis were revealed. The mean percentage of S phase cells was lower, and G2 phase cells was higher in CNE1/pDOR-atm group than in CNE1/pDOR group (P<0.05).


CONCLUSIONS
The mechanisms of cell cycle regulation in radiosensitized CNE1 cells by inhibiting ATM expression might be related with the decreased accumulation of S phase cells and increased accumulation of G2/M phase cells, while have no relationship with G1 arrest and apoptosis.
Wang
Hong-Mei
HM
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
Chen
Long-Hua
LH
Zheng
Xiao-Kang
XK
Wu
Xin-Yao
XY
Xia
Yun-Fei
YF
D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016195:G2 Phase / Q000528:radiation effects; D005822:Genetic Vectors; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics; D011836:Radiation Tolerance; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D016196:S Phase / Q000528:radiation effects; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016372:RNA, Antisense; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases