Association between interleukin‑33 and ovarian cancer

Liu,Xiaoqing; Hansen,Dwayne   M.; Timko,Noah   J.; Zhu,Ziwen; Ames,Andrew; Qin,Chenglu; Nicholl,Michael   B.; Bai,Qian; Chen,Xuhui; Wakefield,Mark   R.; West,Gage; Fang,Yujiang

doi:10.3892/or.2018.6918

Association between interleukin‑33 and ovarian cancer

Authors:
- Xiaoqing Liu
- Dwayne M. Hansen
- Noah J. Timko
- Ziwen Zhu
- Andrew Ames
- Chenglu Qin
- Michael B. Nicholl
- Qian Bai
- Xuhui Chen
- Mark R. Wakefield
- Gage West
- Yujiang Fang
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Affiliations: Department of Anatomy, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui 241000, 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: December 7, 2018 https://doi.org/10.3892/or.2018.6918
Pages: 1045-1050

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Abstract

Ovarian cancer is the leading cause of cancer‑ associated mortality in the female reproductive system. Interleukin (IL)‑33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL‑33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL‑33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL‑33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase‑3 activity kit were all used to evaluate the direct effects of IL‑33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcription‑polymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL‑33; however, the relative caspase‑3 activity in cancer cells was decreased in the presence of IL‑33. Molecular mechanism studies revealed that the pro‑proliferative effect of IL‑33 on cancer cells was associated with decreased levels of p27, and the anti‑apoptotic effect of IL‑33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factor‑related apoptosis‑inducing ligand receptor 1 (TRAILR1). Therefore, IL‑33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an anti‑tumor effort in pancreatic cancer, the results of the present study indicated that IL‑33 exhibited a significant onco‑promoting effect on ovarian cancer. Accordingly, the inhibition of IL‑33 may be a promising therapeutic strategy for ovarian cancer.

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