IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer

Abstract

IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.

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Acknowledgement

We thank Mr. Tyler W. Ball for his help for revision of this manuscript.

Funding

This study was partially supported by grants from Des Moines University for Yujiang Fang (Iowa Science Foundation Grant ISF 16-8, IOER 05-14-01, IOER 112-3749 and IOER 112-3104). This study was also supported by a grant from University of Missouri for Michael B. Nicholl and Yujiang Fang.

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Correspondence to Yujiang Fang.

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Fang, Y., Zhao, L., Xiao, H. et al. IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer. Med Oncol 34, 23 (2017). https://doi.org/10.1007/s12032-016-0880-3

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Keywords

  • IL-33
  • Apoptosis
  • Proliferation