β-elemene inhibits radiation and hypoxia-induced macrophages infiltration via Prx-1/NF-κB/HIF-1α signaling pathway

Abstract

Xiaomu Yu,1,* Zongjuan Li,1,* Yang Zhang,2,* Maoyi Xu,1 Yilin Che,1 Xiaoyuan Tian,1 Ruonan Wang,1 Kun Zou,1 Lijuan Zou11Department of Radiation Oncology, The Second Affiliated Hospital, Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, People’s Republic of China; 2Department of Radiation Oncology, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Yantai, People’s Republic of China *These authors contributed equally to this workBackground: In cancers, tumor-associated macrophages (TAMs) play an important role in the progression, evasion of immunity and sensitivity to therapy. Unfortunately, radiation and hypoxia could induce the M2 macrophages infiltration and polarization.Materials and methods: In this study, we investigated the relevance of macrophage recruitment with radiation and hypoxia by transwell. We also evaluated the effect of β-elemene on the infiltration of M2 macrophages and explored its underlying molecular mechanism by a series of in vitro and in vivo experiments.Results: Irradiated or hypoxia lung cancer cells recruit macrophages, and the recruitment is MCP-1 dependent. We also found that radiation and hypoxia-induced MCP-1 secretion follows upregulation of Prx-1, which leads to nuclear accumulation of NF-κB and HIF-1α expression. In addition, β-elemene could effectively suppress this recruitment phenomenon through Prx-1/NF-κB/HIF-1α signaling.Conclusion: Our study showed that radiation and hypoxia significantly promoted the macrophages recruitment. β-elemene could effectively suppress this recruitment phenomenon and MCP-1 expression via inhibiting Prx-1/NF-κB/HIF-1α pathways.Keywords: β-elemene, radiation, hypoxia, macrophages infiltration, MCP-1, lung cancer

Keywords

• β-elmene
• radiation
• hypoxia
• macrophages infiltration
• MCP-1
• lung cancer