Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition

Abstract

Purpose: Tumor resistance towards radiation has been a big obstacle in the poor prognosis of lung cancer. It has been reported that hypoxia and autophagy partly contribute to this resistance. However, there is controversy over whether autophagy plays a positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance.

Materials and methods: A549 cells were treated with conditioned medium (CM) under 12 h hypoxia or normoxia before irradiation, followed by the measurement of clonogenic survival, reactive oxygen species (ROS), signal of mitochondria and autophagy flux. In some experiments, the A549 cells were respectively transfected with LC3 small interfering RNA (siRNA), or treated with Earle’s Balanced Salt Solution (EBSS).

Results: We found that hypoxia enhanced cell radioresistance by increasing the induction of autophagy. And after hypoxia stress, the number of mitochondria was reduced but the cellular ROS level was enhanced. It was significant that autophagy may enhance cell radioresistance by reducing ROS during hypoxic treatment.

Conclusions: We elucidated the possible mechanisms of autophagy in regulating cancer cell death or survival. These results supply a new opinion about the intrinsic factor of radioresistance of hypoxia tumors.

Keywords:

• Hypoxia
• radioresistance
• autophagy
• ROS
• lung cancer cells

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Notes on contributors

Xiaoyan Chen, Ping Wang and Fei Guo are graduate students.

Xiangdong Wang, Juan Wang, Jinping Xu, and Dexiao Yuan were previous graduate students of Dr. Chunlin Shao. Now Xiangdong Wang, Juan Wang, and Jinping Xu work at hospitals and Dr. Dexiao Yuan is a research assistant at Shao’s laboratory.

Dr. Jianghong Zhang is an associate professor and works on the mechanism of radiation effects on hypoxia tumor cells.

Prof. Chunlin Shao is the head of the Institute and his main research interests are radiation-induced bystander effect and the biomarkers of radiation damage and the process of tumor development.

Additional information

Funding

This work was supported by the National Nature Science Foundation of China [Grant nos. 31570850 and 81672985].