IL‑33 notably inhibits the growth of colon cancer cells

Chen,Xuhui; Lu,Kuanchang; Timko,Noah  J.; Weir,Dylan  M.; Zhu,Ziwen; Qin,Chenglu; Mann,Jeffery D.; Bai,Qian; Xiao,Huaping; Nicholl,Michael  B.; Wakefield,Mark  R.; Fang,Yujiang

doi:10.3892/ol.2018.8728

IL‑33 notably inhibits the growth of colon cancer cells

Authors:
- Xuhui Chen
- Kuanchang Lu
- Noah J. Timko
- Dylan M. Weir
- Ziwen Zhu
- Chenglu Qin
- Jeffery D. Mann
- Qian Bai
- Huaping Xiao
- Michael B. Nicholl
- Mark R. Wakefield
- Yujiang Fang
View Affiliations

Affiliations: Department of Surgery, Luohu Hospital, Shenzhen, Guangdong 518000, P.R. China, Department of Microbiology, Immunology and Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA 50312, USA, Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA
Published online on: May 16, 2018 https://doi.org/10.3892/ol.2018.8728
Pages: 769-774
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Interleukin‑33 (IL‑33), a damage‑associated molecular pattern molecule, is a cytokine within the IL‑1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL‑33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL‑33 on colon cancer cells, based off the previous data that have demonstrated an anti‑tumor effect of IL‑33 on pancreatic cancer cells. The effects of IL‑33 on proliferation, cell survival and apoptosis on human HCT‑116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase‑3 activity kits, terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling staining and immunocytochemistry. It was determined that the HCT‑116 cells demonstrated an notable decrease in optical density value upon incubation with IL‑33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti‑proliferative effect of IL‑33 on HCT‑116 cells was associated with downregulation of the pro‑proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis‑inducing effect of IL‑33 on HCT‑116 cells was associated with downregulation of the anti‑apoptotic molecules Flice‑like inhibitory protein and B‑cell lymphoma 2. Taken together, the results indicated that IL‑33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Brenner H, Kloor M and Pox CP: Colorectal cancer. Lancet. 383:1490–1502. 2014. View Article : Google Scholar : PubMed/NCBI
3	Porta C, Paglino C, Imarisio I and Bonomi L: Cytokine-based immunotherapy for advanced kidney cancer: Past results and future perspectives in the era of molecularly targeted agents. ScientificWorldJournal. 7:837–849. 2007. View Article : Google Scholar : PubMed/NCBI
4	Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, et al: IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 23:479–490. 2005. View Article : Google Scholar : PubMed/NCBI
5	Moussion C, Ortega N and Girard JP: The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: A novel ‘alarmin’? PLoS One. 3:e33312008. View Article : Google Scholar : PubMed/NCBI
6	Jovanovic I, Radosavljevic G, Mitrovic M, Juranic VL, McKenzie AN, Arsenijevic N, Jonjic S and Lukic ML: ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma. Eur J Immunol. 41:1902–1912. 2011. View Article : Google Scholar : PubMed/NCBI
7	Kim W, Kim J, Kim H, Cho H and Kwon B: Association of inhibition of tumor growth with intratumoral hematopoiesis induced by IL-33. J Immunol. 186 Suppl 1:(48): 402011.
8	Duault C, Betous D, Bezombes C, Roga S, Cayrol C, Girard JP, Fournié JJ and Poupot M: IL-33-expanded human Vγ9Vδ2 T cells have anti-lymphoma effect in a mouse tumor model. Eur J Immunol. 47:2137–2141. 2017. View Article : Google Scholar : PubMed/NCBI
9	He Z, Chen L, Souto FO, Canasto-Chibuque C, Bongers G, Deshpande M, Harpaz N, Ko HM, Kelley K, Furtado GC and Lira SA: Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice. Sci Rep. 7:55202017. View Article : Google Scholar : PubMed/NCBI
10	Kim JY, Lim SC, Kim G, Yun HJ, Ahn SG and Choi HS: Interleukin-33/ST2 axis promotes epithelial cell transformation and breast tumorigenesis via upregulation of COT activity. Oncogene. 34:4928–4938. 2015. View Article : Google Scholar : PubMed/NCBI
11	Fang M, Li Y, Huang K, Qi S, Zhang J, Zgodzinski W, Majewski M, Wallner G, Gozdz S, Macek P, et al: IL33 promotes colon cancer cell stemness via JNK activation and macrophage recruitment. Cancer Res. 77:2735–2745. 2017. View Article : Google Scholar : PubMed/NCBI
12	Fang Y, Zhao L, Xiao H, Cook KM, Bai Q, Herrick EJ, Chen X, Qin C, Zhu Z, Wakefield MR and Nicholl MB: IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer. Med Oncol. 34:232017. View Article : Google Scholar : PubMed/NCBI
13	Fang Y, DeMarco VG and Nicholl MB: Resveratrol enhances radiation sensitivity in prostate cancer by inhibiting cell proliferation and promoting cell senescence and apoptosis. Cancer Sci. 103:1090–1098. 2012. View Article : Google Scholar : PubMed/NCBI
14	Fang Y, Yu S and Braley-Mullen H: TGF-β promotes proliferation of thyroid epithelial cells in IFN-γ−/− mice by down-regulation of p21 and p27 via AKT pathway. Am J Pathol. 180:650–660. 2012. View Article : Google Scholar : PubMed/NCBI
15	Fang Y and Braley-Mullen H: Cultured murine thyroid epithelial cells expressing transgenic Fas-associated death domain-like interleukin-1beta converting enzyme inhibitory protein are protected from Fas-mediated apoptosis. Endocrinology. 149:3321–3329. 2008. View Article : Google Scholar : PubMed/NCBI
16	Fang Y, Sharp GC, Yagita H and Braley-Mullen H: A critical role for TRAIL in resolution of granulomatous experimental autoimmune thyroiditis. J Pathol. 216:505–513. 2008. View Article : Google Scholar : PubMed/NCBI
17	Fang Y, Wei Y, DeMarco V, Chen K, Sharp GC and Braley-Mullen H: Murine FLIP transgene expressed on thyroid epithelial cells promotes resolution of granulomatous experimental autoimmune thyroiditis in DBA/1 mice. Am J Pathol. 170:875–887. 2007. View Article : Google Scholar : PubMed/NCBI
18	Fang Y, Chen X, Bai Q, Qin C, Mohamud AO, Zhu Z, Ball TW, Ruth CM, Newcomer DR, Herrick EJ and Nicholl MB: IL-9 inhibits HTB-72 melanoma cell growth through upregulation of p21 and TRAIL. J Surg Oncol. 111:969–974. 2015. View Article : Google Scholar : PubMed/NCBI
19	Nicholl MB, Chen X, Qin C, Bai Q, Zhu Z, Davis MR and Fang Y: IL-32α has differential effects on proliferation and apoptosis of human melanoma cell lines. J Surg Oncol. 113:364–369. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zhu Z, Davidson KT, Brittingham A, Wakefield MR, Bai Q, Xiao H and Fang Y: Trichomonas vaginalis: A possible foe to prostate cancer. Med Oncol. 33:1152016. View Article : Google Scholar : PubMed/NCBI
21	Zhang Y, Davis C, Shah S, Hughes D, Ryan JC, Altomare D and Peña MM: IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis. Mol Carcinog. 56:272–287. 2017. View Article : Google Scholar : PubMed/NCBI
22	Griesenauer B and Paczesny S: The ST2/iL-33 Axis in immune cells during inflammatory diseases. Front Immunol. 8:752017. View Article : Google Scholar : PubMed/NCBI
23	Lock FE, Babaian A, Zhang Y, Gagnier L, Kuah S, Weberling A, Karimi MM and Mager DL: A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer. PLoS One. 12:e01806592017. View Article : Google Scholar : PubMed/NCBI
24	Liew FY, Pitman NI and McInnes IB: Disease-associated functions of IL-33: The new kid in the IL-1 family. Nat Rev Immunol. 10:103–110. 2010. View Article : Google Scholar : PubMed/NCBI
25	Nicholl MB, Ledgewood CL, Chen X, Bai Q, Qin C, Cook KM, Herrick EJ, Diaz-Arias A, Moore BJ and Fang Y: Il-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: Evidence for a role as an autocrine growth factor. Cytokine. 70:126–133. 2014. View Article : Google Scholar : PubMed/NCBI
26	Zhang D, Li X, Chen C, Li Y, Zhao L, Jing Y, Liu W, Wang X, Zhang Y, Xia H, et al: Attenuation of p38-mediated miR-1/133 expression facilitates myoblast proliferation during the early stage of muscle regeneration. PLoS One. 7:e414782012. View Article : Google Scholar : PubMed/NCBI
27	Zhu Z, Zhang D, Lee H, Menon AA, Wu J, Hu K and Jin Y: Macrophage-derived apoptotic bodies promote the proliferation of the recipient cells via shuttling microRNA-221/222. J Leukoc Biol. 101:1349–1359. 2017. View Article : Google Scholar : PubMed/NCBI
28	Griffith TS, Brunner T, Fletcher SM, Green DR and Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 270:1189–1192. 1995. View Article : Google Scholar : PubMed/NCBI