Medical Oncology

, 34:23 | Cite as

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

  • Yujiang FangEmail author
  • Lei Zhao
  • Huaping Xiao
  • Kathryn M. Cook
  • Qian Bai
  • Elizabeth J. Herrick
  • Xuhui Chen
  • Chenglu Qin
  • Ziwen Zhu
  • Mark R. Wakefield
  • Michael B. Nicholl
Original Paper


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.


IL-33 Apoptosis Proliferation 



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


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.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yujiang Fang
    • 1
    • 2
    Email author
  • Lei Zhao
    • 3
  • Huaping Xiao
    • 1
    • 5
  • Kathryn M. Cook
    • 2
  • Qian Bai
    • 2
  • Elizabeth J. Herrick
    • 2
  • Xuhui Chen
    • 1
    • 6
  • Chenglu Qin
    • 2
    • 6
  • Ziwen Zhu
    • 2
  • Mark R. Wakefield
    • 2
  • Michael B. Nicholl
    • 2
    • 4
  1. 1.Department of Microbiology, Immunology and Pathology, College of Osteopathic MedicineDes Moines UniversityDes MoinesUSA
  2. 2.Department of SurgeryUniversity of Missouri School of MedicineColumbiaUSA
  3. 3.Department of Infectious DiseaseThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
  4. 4.Department of SurgerySouth Texas Veterans Health Care SystemSan AntonioUSA
  5. 5.The Affiliated Hospital of Xiangnan UniversityChenzhouChina
  6. 6.Luohu HospitalShenzhenChina

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