Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma

Yu,Shuang; Yin,Jian‑Jian; Miao,Jin‑Xin; Li,Shi‑Gang; Huang,Chen‑Zheng; Huang,Ning; Fan,Tian‑Li; Li,Xiang‑Nan; Wang,Yao‑He; Han,Sheng‑Na; Zhang,Li‑Rong

doi:10.3892/or.2020.7493

Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma

Authors:
- Shuang Yu
- Jian‑Jian Yin
- Jin‑Xin Miao
- Shi‑Gang Li
- Chen‑Zheng Huang
- Ning Huang
- Tian‑Li Fan
- Xiang‑Nan Li
- Yao‑He Wang
- Sheng‑Na Han
- Li‑Rong Zhang
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Affiliations: Department of Pharmacology, Basic Medical School, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, Department of Science and Technology, Henan University of Chinese Medicine, Zhengzhou, Henan 450001, P.R. China, Department of Clinical Medicine, School of Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Thoracic Surgery, The First Clinical Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, National Centre for International Research in Cell and Gene Therapy, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: February 7, 2020 https://doi.org/10.3892/or.2020.7493
Pages: 1113-1124
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inflammasomes can identify endogenous danger signals as an inflammatory immune response. As the most common inflammasome, the NLR pyrin family domain containing 3 (NLRP3) inflammasome is associated with the pathogenesis of different tumors. However, the function of the NLRP3 inflammasome in esophageal cancer (EC) has rarely been reported. Herein, the expression levels of the components of NLRP3 inflammasome and Ki‑67 were analyzed by immunohistochemistry. Furthermore, correlations between the NLRP3 inflammasome and Ki‑67 along with the clinicopathological features of EC patients were evaluated. The components of the NLRP3 inflammasome were also assessed by western blot analysis and quantitative PCR. NLRP3 was silenced or overexpressed in different esophageal squamous cell carcinoma (ESCC) cell lines, and cell viability, migration and invasion were assessed by CCK‑8 and Transwell assays. The present results showed that high NLRP3 expression in the tumor specimens was significantly associated with TNM stage and T category. Spearman's correlation analysis revealed a positive correlation between NLRP3 and the Ki‑67 proliferation index. The mRNA and protein levels of NLRP3, apoptosis‑associated speck‑like protein containing a CARD (ASC), cleaved caspase‑1, and interleukin (IL)‑1β in tumor tissues were higher than those in non‑cancerous tissues. The level of secreted IL‑1β in tumor tissues was also increased, as compared to that in normal tissues. Silencing of NLRP3 in KYSE‑70 and TE13 cells strongly attenuated cell viability, decreased cell mobility in wound‑healing assays and greatly diminished the ability of cell migration and invasion in the Transwell system. Overexpression of NLRP3 in KYSE‑510 and EC9706 cells markedly promoted the proliferation, migration and invasion. Collectively, these results revealed that the the NLRP3 inflammasome is upregulated in human ESCC tissues and promotes ESCC progression. Hence, NLRP3 could be a promising new candidate diagnostic and prognostic target.

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