抑制甲酰肽受体1活性可抑制肺腺癌细胞在缺氧条件下的致瘤性，并减弱其侵袭和迁移能力。

Inhibition of formyl peptide receptor 1 activity suppresses tumorigenicity and attenuates the invasion and migration of lung adenocarcinoma cells under hypoxic conditions .

作者信息

Huang Bo, Guo Hongrong, Ding Jie, Li Jun, Wang Hongjuan, Xu Jianqun, Zheng Quan, Zhou Lijun, Dai Qin

机构信息

Department of Respiration, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China.

Department of Nephrology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China.

出版信息

Ann Transl Med. 2020 Sep;8(18):1174. doi: 10.21037/atm-20-5864.

DOI:10.21037/atm-20-5864

PMID:33241023

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7576028/

Abstract

BACKGROUND

Tumor hypoxia has been widely reported to promote metastasis. However, the molecular mechanisms underlying metastasis-associated hypoxia remain unclear. Formyl peptide receptor 1 (FPR1) has been reported to be highly expressed under hypoxic conditions. This study aimed to explore the role of FPR1 in tumor cells under hypoxic conditions.

METHODS

The expressions of FPR1 and hypoxia-inducible factor 1α (HIF-1α) in A549 cells under hypoxic conditions were detected using western blot. The expression of FPR1 in A549 cells under hypoxic conditions was suppressed using the FPR1 antagonist Boc2. Wound-healing and Transwell assays were performed to investigate the migration and invasion of cells. Furthermore, the tumorigenicity of A549 cells was evaluated by constructing a hypoxic mouse model of lung adenocarcinoma. The expression levels of HIF-1α and FPR1 in tumors were measured by real-time polymerase chain reaction (PCR) and western blot.

RESULTS

The expression levels of FPR1 and HIF-1α increased in a time-dependent manner after exposure to hypoxic conditions. Wound-healing and Transwell assays showed that hypoxia promoted the migration and invasion abilities of A549 cells, whereas downregulation of FPR1 blocked the effects of hypoxia on A549 cells. Our in vivo results demonstrated that the tumor volumes and weights of mice exposed to hypoxic conditions were significantly higher than those of untreated mice. Furthermore, the downregulation of FPR1 blocked the effects of hypoxia in the mice. Meanwhile, the expressions of HIF-1α and FPR1 at the protein and mRNA levels were increased after hypoxic exposure, whereas FPR1 antagonist Boc2 suppressed the effect of hypoxia on the expression of FPR1.

CONCLUSIONS

Our results suggest that FPR1 could be a therapeutic target for suppressing the invasion and tumorigenicity of lung adenocarcinoma cells.

摘要

背景

肿瘤缺氧已被广泛报道可促进转移。然而，与转移相关的缺氧的分子机制仍不清楚。据报道，甲酰肽受体1（FPR1）在缺氧条件下高表达。本研究旨在探讨FPR1在缺氧条件下对肿瘤细胞的作用。

方法

采用蛋白质印迹法检测缺氧条件下A549细胞中FPR1和缺氧诱导因子1α（HIF-1α）的表达。使用FPR1拮抗剂Boc2抑制缺氧条件下A549细胞中FPR1的表达。进行伤口愈合和Transwell实验以研究细胞的迁移和侵袭。此外，通过构建肺腺癌缺氧小鼠模型评估A549细胞的致瘤性。通过实时聚合酶链反应（PCR）和蛋白质印迹法测量肿瘤中HIF-1α和FPR1的表达水平。

结果

暴露于缺氧条件后，FPR1和HIF-1α的表达水平呈时间依赖性增加。伤口愈合和Transwell实验表明，缺氧促进了A549细胞的迁移和侵袭能力，而FPR1的下调则阻断了缺氧对A549细胞的影响。我们的体内结果表明，暴露于缺氧条件下的小鼠的肿瘤体积和重量显著高于未处理的小鼠。此外，FPR1的下调阻断了缺氧对小鼠的影响。同时，缺氧暴露后HIF-1α和FPR1在蛋白质和mRNA水平的表达增加，而FPR1拮抗剂Boc2抑制了缺氧对FPR1表达的影响。