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The effects of NLRP3 inflammasome inhibition by MCC950 on LPS-induced pancreatic adenocarcinoma inflammation

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells.

Methods

The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.

Results

LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.

Conclusion

There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.

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Acknowledgements

This work was supported by International Medical University [project no.: MMM 1-2019(02)].

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Authors and Affiliations

  1. School of Postgraduate Studies, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

    Alan Cheuk Keong Yaw & Jeremy Kean Yi Yap

  2. Institute for Research, Development and Innovation, International Medical University, Jalan Jalil Perkasa 19, 126 Jalan 19/155B, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

    Elaine Wan Ling Chan

  3. Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

    Chun Wai Mai

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  1. Alan Cheuk Keong Yaw
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Contributions

EWLC and CWM are involved in conceptualisation; EWLC is involved in methodology development; ACKY and JKYY are involved in formal analysis; and EWLC, CWM, ACKY and JYKY are involved in writing review and editing. All the authors agreed to the final manuscript.

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Correspondence to Elaine Wan Ling Chan.

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Yaw, A.C.K., Chan, E.W.L., Yap, J.K.Y. et al. The effects of NLRP3 inflammasome inhibition by MCC950 on LPS-induced pancreatic adenocarcinoma inflammation. J Cancer Res Clin Oncol 146, 2219–2229 (2020). https://doi.org/10.1007/s00432-020-03274-y

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