The Effect of Autophagy on the Radioresistance 
of Human Adenocarcinoma A549 Cell in Hypoxia Condition

Abstract

Background and objective 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. Methods 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. Results 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. Conclusion The level of protective autophagy of A549 cells increased in hypoxia condition; thus, inhibiting autophagy improves the radiosensitivity of A549 cells.

Keywords

• Lung neoplasms
• Autophagy
• Hypoxia
• 3-Methyladenine (3-MA)
• Radiation tolerance