Display options
Share it on

Cancer Manag Res. 2017 Oct 09;9:481-493. doi: 10.2147/CMAR.S147699. eCollection 2017.

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

Cancer management and research

Jiachi Ma, Xiaowen Sun, Tiankang Guo, He Su, Quan Chen, Zhenqiang Gong, Jianbo Qi, Xiaodan Zhao

Affiliations

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

PMID: 29062241 PMCID: PMC5640395 DOI: 10.2147/CMAR.S147699

Abstract

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 (

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

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

References

  1. Int J Cancer. 1995 Mar 3;60(5):712-7 - PubMed
  2. Int J Mol Sci. 2013 Sep 12;14(9):18824-49 - PubMed
  3. Oncol Lett. 2015 Apr;9(4):1641-1646 - PubMed
  4. J Steroid Biochem Mol Biol. 2015 Feb;146:62-73 - PubMed
  5. J Biochem. 2015 May;157(5):271-84 - PubMed
  6. Cancer Microenviron. 2015 Dec;8(3):187-200 - PubMed
  7. Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25 - PubMed
  8. Urol Oncol. 2007 Sep-Oct;25(5):407-11 - PubMed
  9. J Surg Oncol. 2009 May 1;99(6):361-7 - PubMed
  10. Clin Cancer Res. 2008 Nov 1;14(21):6735-41 - PubMed
  11. World J Gastroenterol. 2017 Jul 28;23 (28):5167-5178 - PubMed
  12. Cancer Growth Metastasis. 2014 Jun 02;7:9-18 - PubMed
  13. Toxicol Lett. 1998 Dec 28;102-103:227-34 - PubMed
  14. Cancer Res. 2007 Jul 15;67(14):6854-62 - PubMed
  15. Sci Rep. 2016 Oct 27;6:36107 - PubMed
  16. J Natl Cancer Inst. 1990 Jan 3;82(1):4-6 - PubMed
  17. J Surg Oncol. 2010 Oct 1;102(5):469-77 - PubMed
  18. Haematologica. 2013 Jul;98(7):1132-41 - PubMed
  19. Nature. 2001 May 17;411(6835):375-9 - PubMed
  20. J Exp Clin Cancer Res. 2000 Dec;19(4):497-504 - PubMed
  21. Cancer Lett. 2003 Feb 10;190(1):105-12 - PubMed
  22. Mol Med. 2014 Dec 16;20 Suppl 1:S43-58 - PubMed
  23. Cancer Lett. 2015 Aug 28;365(1):11-22 - PubMed
  24. J Cell Biol. 1992 Nov;119(3):629-41 - PubMed
  25. Front Physiol. 2014 Mar 28;5:114 - PubMed
  26. Int J Cancer. 2011 May 1;128(9):2038-49 - PubMed
  27. Biochem J. 2008 Feb 1;409(3):635-49 - PubMed
  28. Cancer Res. 1997 Aug 1;57(15):3305-13 - PubMed
  29. J Intern Med. 2017 Jan;281(1):75-85 - PubMed
  30. J Immunol. 2012 Dec 15;189(12):5533-40 - PubMed
  31. Cell. 1991 Nov 29;67(5):901-8 - PubMed
  32. Nat Rev Cancer. 2004 Jul;4(7):540-50 - PubMed
  33. Medicine (Baltimore). 2017 Mar;96(11):e6370 - PubMed
  34. J Surg Res. 2008 Aug;148(2):197-204 - PubMed
  35. Transl Stroke Res. 2016 Oct;7(5):395-406 - PubMed
  36. Expert Opin Ther Targets. 2012 Jun;16(6):553-72 - PubMed

Publication Types