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白细胞介素-1 受体拮抗剂通过阻断白细胞介素-1α 抑制食管癌细胞生长。

IL-1RA suppresses esophageal cancer cell growth by blocking IL-1α.

机构信息

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.

出版信息

J Clin Lab Anal. 2019 Jul;33(6):e22903. doi: 10.1002/jcla.22903. Epub 2019 May 17.

DOI:10.1002/jcla.22903
PMID:31102307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6642324/
Abstract

BACKGROUND

Interleukin-1 promotes tumor angiogenesis through VEGF production. The interleukin-1 receptor antagonist can suppress tumors by blocking this effect.

METHODS

Immunohistochemistry, WB, and gene sequencing were used to analyze the expression of IL-1RA in esophageal cancer patients. WB was used to detect the expression of IL-1RA and interleukin-1α in esophageal cancer cells. Stable ESCC cell models overexpressing the IL-1RA were constructed. Their cell functions were tested, and their effects on VEGF were examined.

RESULTS

IL-1RA is downregulated in primary EC tumors, and this downregulation of IL-1RA is closely related to TNM staging and survival prognosis. The overexpression of IL-1RA increased the proliferation of KYSE410 EC cells, which have a high level of IL-1α expression. Overexpression of IL-1RA in KYSE410 cells promotes a decrease in the expression of VEGF-A. However, IL-1RA expression did not cause any changes in EC9706 cells with low IL-1α expression.

CONCLUSION

IL-1RA acts as a tumor suppressor, and its deletion promotes tumor progression by increasing VEGF-A expression in ESCC.

摘要

背景

白细胞介素-1 通过促进血管内皮生长因子(VEGF)的产生来促进肿瘤血管生成。白细胞介素-1 受体拮抗剂可通过阻断这种作用来抑制肿瘤。

方法

采用免疫组织化学、WB 和基因测序分析食管癌患者中 IL-1RA 的表达。采用 WB 检测食管癌细胞中 IL-1RA 和白细胞介素-1α 的表达。构建 IL-1RA 过表达的稳定 ESCC 细胞模型。测试其细胞功能,并检测其对 VEGF 的影响。

结果

IL-1RA 在原发性 EC 肿瘤中表达下调,IL-1RA 的下调与 TNM 分期和生存预后密切相关。IL-1RA 的过表达增加了 IL-1α 表达水平较高的 KYSE410 EC 细胞的增殖。在 KYSE410 细胞中过表达 IL-1RA 会导致 VEGF-A 的表达降低。然而,在 IL-1α 表达水平较低的 EC9706 细胞中,IL-1RA 的表达并未引起任何变化。

结论

IL-1RA 作为一种肿瘤抑制因子,其缺失通过增加 ESCC 中 VEGF-A 的表达促进肿瘤进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7541/6642324/3d1a4af675aa/JCLA-33-e22903-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7541/6642324/7cb77785af5d/JCLA-33-e22903-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7541/6642324/b8a0010ba2ed/JCLA-33-e22903-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7541/6642324/3d1a4af675aa/JCLA-33-e22903-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7541/6642324/7cb77785af5d/JCLA-33-e22903-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7541/6642324/b8a0010ba2ed/JCLA-33-e22903-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7541/6642324/3d1a4af675aa/JCLA-33-e22903-g003.jpg

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