The effect of autophagy on the radioresistance of human adenocarcinoma A549 cell in hypoxia condition

• Published in: Zhongguo fei ai za zhi 2012-11, Vol.15 (11), p.638-641
• Main Authors: Li, Yong, Xu, Liyao, Cai, Aqiao, Li, Lifang, Zhong, Xiaojun
• Format: Article
• Language: Chinese
• Subjects: 3-Methyladenine (3-MA); Adenine - analogs & derivatives; Adenine - pharmacology; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Autophagy; Autophagy - drug effects; Autophagy - radiation effects; Cell Hypoxia - drug effects; Cell Hypoxia - radiation effects; Cell Line, Tumor; Gamma Rays; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Humans; Hypoxia; Lung cancer; Lung neoplasms; Lung Neoplasms - pathology; Microtubule-Associated Proteins - metabolism; Radiation therapy; Radiation tolerance; Radiation Tolerance - drug effects
• ISSN: 1009-3419; 1999-6187
• DOI: 10.3779/j.issn.1009-3419.2012.11.06

It has been proven that cancer cell autophagy can be induced by hypoxia. In addition, autophagy was correlated with radiosensitivity. Thus, regulating the autophagy signaling pathway is a potential treatment strategy. The aim of this study is to investigate the effects of combined autophagy inhibitor 3-methyladenine (3-MA) on the radiosensitivity of human adenocarcinoma A549 cells in hypoxia condition. A549 cells were cultured in hypoxia condition, and then divided into two groups: hypoxia group and 3-MA plus hypoxia group. Electronic microscopy was used to detect autophagosome levels at different time points. The expression of LC3 was examined by Western blot. The proliferation activity of A549 cells after radiotherapy (0 Gy, 2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy) was determined with an MTT assay. Autophagosome formation and the LC3II/LC3I ratio increased under hypoxic conditions. After treatment with the autophagy inhibitor 3-MA, the quantity of autophagosomes and the LC3II/LC3I ratio decreased. The proliferative activity of the cells in the 3-MA plus hypoxia group was remarkably lower than that in the hypoxia group after treatment with radiotherapy. The level of protective autophagy of A549 cells increased in hypoxia condition; thus, inhibiting autophagy improves the radiosensitivity of A549 cells.