Frontiers in Oncology (2020-08-01)

Immune Cells Combined With NLRP3 Inflammasome Inhibitor Exert Better Antitumor Effect on Pancreatic Ductal Adenocarcinoma

  • Hailiang Liu,
  • Yong Xu,
  • Kai Liang,
  • Rong Liu

DOI
https://doi.org/10.3389/fonc.2020.01378
Journal volume & issue
Vol. 10

Abstract

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Pancreatic cancer is among the most aggressive malignancies associated with chronic inflammation. Moreover, cellular immunity can be inhibited by inflammation induced by nucleotide-binding domain, leucine-rich family, pyrin-containing 3 (NLRP3) inflammasome. Accordingly, NLRP3 inhibition combining cytokine-induced killer (CIK) cells may improve antitumor efficacy. 3,4-Methylenedioxy-β-nitrostyrene (MNS) was selected as a specific NLRP3 inflammasome inhibitor. Western blot was used to evaluate the NLRP3 inflammasome expression in pancreatic cancer cell lines SW1990 and PANC-1. The impact of NLRP3 inhibition on migration, invasiveness, and proliferation of pancreatic cancer cells was analyzed through wound healing assay, Transwell assay, and Cell Counting Kit-8 (CCK-8) assay, respectively. The combining antitumor effect in vivo of CIK and NLRP3 inhibition was evaluated in a subcutaneous human pancreatic cancer BALB/c nude mouse model. Western blot analysis showed significant expression of NLRP3 inflammasome in human pancreatic cancer lines SW1990 and PANC-1, and MNS did significantly inhibit the expression of NLRP3 inflammasome in cell lines. Moreover, NLRP3 inhibition could significantly decrease the migration, invasiveness, and proliferation of pancreatic cancer cells. In vivo experiments showed that combination treatment with MNS and CIK cells had the greatest antitumor effect among the four treatment groups including control, MNS, and CIK. Combination treatment with NLRP3 inflammasome inhibition and CIK cells showed greater antitumor efficacy through inflammation inhibition and immunity restoration.

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