Research Paper|Volume 13, Issue 2|pp 2575—2592

β-Elemene enhances radiosensitivity in non-small-cell lung cancer by inhibiting epithelial–mesenchymal transition and cancer stem cell traits via Prx-1/NF-kB/iNOS signaling pathway

Kun Zou¹, Zongjuan Li¹, Yang Zhang³, Lin Mu¹, Miao Chen², Ruonan Wang¹, Wuguo Deng², Lijuan Zou¹, Jiwei Liu¹

¹The First Affiliated Hospital, Institute of Cancer Stem Cell and, The Second Affiliated Hospital, Dalian Medical University, Dalian, China
²Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
³Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Yantai, China

* Equal contribution

Received: September 26, 2019Accepted: September 3, 2020Published: December 9, 2020

https://doi.org/10.18632/aging.202291

Copyright: © 2021 Zou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Radiation therapy is widely used to treat a variety of malignant tumors, including non-small-cell lung cancer (NSCLC). However, ionizing radiation (IR) paradoxically promotes radioresistance, metastasis and recurrence by inducing epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Here, we developed two NSCLC radioresistant (RR) cell lines (A549-RR and H1299-RR) and characterized their motility, cell cycle distribution, DNA damage, and CSC production using migration/invasion assays, flow cytometry, comet assays, and sphere formation, respectively. We also evaluated their tumorigenicity in vivo using a mouse xenograft model. We found that invasion and spheroid formation by A549-RR and H1299-RR cells were increased as compared to their parental cells. Furthermore, as compared to radiation alone, the combination of β-elemene administration with radiation increased the radiosensitivity of A549 cells and reduced expression of EMT/CSC markers while inhibiting the Prx-1/NF-kB /iNOS signaling pathway. Our findings suggest that NSCLC radioresistance is associated with EMT, enhanced CSC phenotypes, and activation of the Prx-1/NF-kB/iNOS signaling pathway. They also suggest that combining β-elemene with radiation may be an effective means of overcoming radioresistance in NSCLC.