Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway

Journal of Experimental & Clinical Cancer Research

Laiyu Liu¹  Wenqi Huang¹  Jihong Huang¹  Lu Yuan¹  Yuting Wu¹  Zici Wang²  Huazhen Liang³  Shaoqun Li⁴  Mi Yang⁵  Longshan Zhang⁵  Jian Guan⁵  Xixi Wu⁵  Xiaoqing Wang⁵  Yin Wang⁵  Hua Pan⁵  Weiqiang Huang⁵  Liwei Liao⁵ 

[1] Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China;Department of Oncology, Maoming People’s Hospital, Maoming, Guangdong, China;Department of Radiation Oncology, Guangdong 999 Brain Hospital, Guangzhou, Guangdong, China;Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;

关键词: Nasopharyngeal carcinoma;    Cancer-associated fibroblast;    Irradiation;    IL-8;    NF-κB pathway;    Tranilast;   

DOI  :  10.1186/s13046-021-01878-x

来源: Springer

【 摘 要 】

BackgroundIrradiation has emerged as a valid tool for nasopharyngeal carcinoma (NPC) in situ treatment; however, NPC derived from tissues treated with irradiation is a main cause cancer-related death. The purpose of this study is to uncover the underlying mechanism regarding tumor growth after irradiation and provided potential therapeutic strategy.MethodsFibroblasts were extracted from fresh NPC tissue and normal nasopharyngeal mucosa. Immunohistochemistry was conducted to measure the expression of α-SMA and FAP. Cytokines were detected by protein array chip and identified by real-time PCR. CCK-8 assay was used to detect cell proliferation. Radiation-resistant (IRR) 5-8F cell line was established and colony assay was performed to evaluate tumor cell growth after irradiation. Signaling pathways were acquired via gene set enrichment analysis (GSEA). Comet assay and γ-H2AX foci assay were used to measure DNA damage level. Protein expression was detected by western blot assay. In vivo experiment was performed subcutaneously.ResultsWe found that radiation-resistant NPC tissues were constantly infiltrated with a greater number of cancer-associated fibroblasts (CAFs) compared to radiosensitive NPC tissues. Further research revealed that CAFs induced the formation of radioresistance and promoted NPC cell survival following irradiation via the IL-8/NF-κB pathway to reduce irradiation-induced DNA damage. Treatment with Tranilast, a CAF inhibitor, restricted the survival of CAF-induced NPC cells and attenuated the of radioresistance properties.ConclusionsTogether, these data demonstrate that CAFs can promote the survival of irradiated NPC cells via the NF-κB pathway and induce radioresistance that can be interrupted by Tranilast, suggesting the potential value of Tranilast in sensitizing NPC cells to irradiation.

【 授权许可】

CC BY