Mechanism of radiosensitization of 3-methyladenine in human hypopharynx cancer cells
10.3760/cma.j.issn.1673-0860.2012.11.013
- VernacularTitle:3-甲基腺嘌呤对人下咽癌细胞的放射增敏效应及其机制研究
- Author:
Zhi-Ping TANG
1
;
Yao-Dong XU
;
Jie-Ren PENG
;
Yong-Kang OU
;
Zhong GUAN
Author Information
1. 中山大学孙逸仙纪念医院耳鼻咽喉头颈外科
- Keywords:
Hypopharyngeal neoplasms;
Adenine;
Radiation tolerance;
DNA damage;
Cell cycle
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2012;47(11):937-941
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the radiosensitizing effect and its mechanism of 3-MA in human hypopharynx cancer cells.Methods Fadu cells were treated with 5 mmol/L of 3-MA combined with 2 Gy or 4 Gy of X-ray and cell cloning efficiency and DNA lesion severity (tail moment) were examined by clonogenic survival assay and comet assay.Cell cycle distributions of Fadu cells treated with different doses of 3-MA(1,2,5,10 mmol/L) were detected by flow cytometer.The expressions of p62 and cyclin B1 were examined by western blot.Results The cloning efficiency and DNA lesion severity of cells treated with 3-MA alone showed no notable changes.However,3-MA enhanced significantly the inhibitory effects of X-ray (2 Gy or 4 Gy) on cloning efficiency of the cells (t =13.41 or 13.98,P ＜ 0.001),and the cells showed more serious DNA damages (t =7.07 or 6.91,P ＜ 0.001).The mean G2/M percentages of control cells and the cells treated with 1,2,5,10 mmol/L of 3-MA were (17.10 ± 1.20) ％,(23.30 ± 2.3) ％,(39.90 ± 3.12)％,(58.47 ± 1.65)％ and (76.13 ± 3.51)％,respectively,and differences among groups were statistically significant(F =278.4,P ＜ 0.05).The expression of p62 in cells treated with 3-MA showed a dose-dependent increase,while cyclin B1 showed a dose-dependent decrease.Conclusion The autophagy inhibitor 3-MA could enhance radiosensitivity of human hypopharynx cancer cells by inducing G2/M arrest and enhancing irradiation-induced DNA damage.
