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Interleukin-1 receptor antagonist inhibits angiogenesis via blockage IL-1α/PI3K/NF-κB pathway in human colon cancer cell

Authors Ma J, Sun X, Guo T, Su H, Chen Q, Gong Z, Qi J, Zhao X

Received 29 July 2017

Accepted for publication 6 September 2017

Published 9 October 2017 Volume 2017:9 Pages 481—493

DOI https://doi.org/10.2147/CMAR.S147699

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Nakshatri


Jiachi Ma,1 Xiaowen Sun,2 Tiankang Guo,1 He Su,1 Quan Chen,1 Zhenqiang Gong,3 Jianbo Qi,3 Xiaodan Zhao3

1Department of General Surgery, Gansu Provincial People’s Hospital, LanZhou, 2Department of Dermatology, The First Hospital of Tianshui, Tianshui, 3Ningxia Medical University Graduate School of Medical Sciences, Surgical Oncology, Yinchuan, People’s Republic of China

Purpose: This article investigates the relationship between cancer cells and stromal cells in carcinoma cell living microenvironment and elucidates the mechanism that interleukin-1 receptor antagonist (IL-1RA) blocks metastatic potential in colon cancer.
Methods: Western blot and RT-PCR assay were used to determine the expression of hepatocyte growth factor (HGF) and IL-1α in colon carcinoma cells and stromal cells. Effect of IL-1RA and HGF on metastatic potential of colon cancer cells were examined by proliferation, invasion, and angiogenesis assays. The interactional role of IL-1RA and HGF were detected by ELISA assay, invasion, and angiogenesis assay making up a co-culture system consisting of stromal and colon cancer cells in cells living microenvironment.
Results: IL-1α was expressed in human umbilical vein endothelial cells (HUVECs) and HT-29 and WiDr (colon cancer cell lines with higher liver metastatic potential). HGF was expressed only in fibroblast. HGF secretion from fibroblasts was significantly inhibited by IL-1RA (P<0.01). Furthermore, IL-1RA could significantly inhibit migration, proliferation, and angiogenesis of HUVECs (P<0.01). In the double co-culture system, there is a high liver metastatic potential of colon cancer cell line (HT-29) because it can secrete autocrine IL-1α, significantly enhanced angiogenesis compared with low liver metastatic cell line (CaCo-2) (P<0.01), which does not secrete IL-1α. On the contrary, blockage of autocrine IL-1α by IL-1RA might significantly decrease metastatic potential of colon carcinoma cells through downregulation of IL-1α/PI3K/NF-κB pathway.
Conclusion: IL-1 receptor antagonist (IL-1RA) is an important inhibitor in metastatic process of colon carcinoma cell. Based on the above results, we suggest that IL-1RA may be a promising new therapeutic approach in inhibiting colon cancer with IL-1-producing patients.

Keywords: interleukin receptor antagonist, hepatocyte growth factor, metastasis, angiogenesis, colon cancer, IL-1RA, HGF, angiogenesis, colon carcinoma

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