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International Journal of Clinical Oncology

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Open Access 01-08-2018 | Original Article

Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer

Authors: Zhenqiang Gong, Jiachi Ma, He Su, Tiankang Guo, Hui Cai, Quan Chen, Xiaodan Zhao, Jianbo Qi, Jianbo Du

Published in: International Journal of Clinical Oncology | Issue 4/2018

Abstract

Background

Interleukin-1 alpha (IL-1α) plays an important role in tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the interactions of tumor cells and their micro-environment is poorly understood. We have evaluated the role of IL-1RA in the metastatic process as well as the mutual or reciprocal actions between gastric cancer cells and stromal cells.

Materials and methods

The expressions of IL-1α, vascular endothelial growth factor (VEGF), and IL-1RI mRNA were determined by reverse transcriptase-PCR. The regulatory effect of IL-1RA on the secretion of VEGF in human gastric cancer cells and human umbilical vein endothelial cells (HUVECs) was detected by enzyme-linked immunosorbent assay. The effect of IL-1RA on metastatic potential was evaluated using proliferation, invasion, and angiogenesis assays, respectively, including in vitro co-culture system models consisting of tumor cells and stromal cells that were used to detect invasion and angiogenesis.

Results

Interleukin-1α mRNA was detected in the higher liver metastatic gastric cell line MKN45. IL-1α protein was expressed in MKN45 cells and in HUVECs. VEGF mRNA and protein were detected in the three gastric cancer cell lines (MKN4, NUGC-4, and AGS). Levels of VEGF secreted by gastric cancer cells and HUVECs appeared to be reduced through the action of IL-1RA via IL-1RI in a dose-dependent manner (P < 0.01). IL-1RA significantly inhibited the proliferation and migration of HUVECs (P < 0.01) and tube formation by HUVECs (P < 0.01), both in a dose-dependent manner. Compared with HUVECs grown without cancer cells (control) or with NUGC-4 cells, tube formation by HUVECs was significantly enhanced by co-culture with MKN45 cells (P < 0.01). The enhanced tube formation in the presence of MKN45 cells was inhibited by the addition of IL-1RA (P < 0.01).

Conclusions

The IL-1RA downregulated the metastatic potential of gastric cancer through blockage of the IL-1α/VEGF signaling pathways. IL-1RA has the potential to play a role in the treatment of gastric cancer.

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Title: Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer
Authors: Zhenqiang Gong
Jiachi Ma
He Su
Tiankang Guo
Hui Cai
Quan Chen
Xiaodan Zhao
Jianbo Qi
Jianbo Du
Publication date: 01-08-2018
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 4/2018
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-018-1242-2

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Abstract

Background

Materials and methods

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Conclusions

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