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PO1-8-25

The role of NLRP3 inflammasome in regulating the progression of prostate cancer

[Speaker] Hsin-En Wu:1
[Co-author] Chia-Yang Li:1
1:Graduate Institute of Medicine, College of Medicine, Chia-Yang Li Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Chronic inflammation is a hallmark of cancers and plays a critical role in modulating tumor progression and metastasis. Inflammasomes are a group of cytosolic protein complexes, composed of an NOD-like protein (NLR), the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1, which are responsible for the cleavage of pro-IL-1 beta and pro-IL-18 proteins into mature and biologically active IL-1 beta and IL-18, respectively. Mature IL-1 beta is a potent proinflammatory mediator in many immune reactions, including the recruitment of innate immune cells to the site of infection and modulation of adaptive immune cells adaptive immune cells, whereas mature IL-18 is important for the production of IL-12 and IL- 15 and regulation of both Th1 and Th2 responses. Previous study indicated that increased concentration of IL-1 beta protein in tumor tissues is associated with poor prognosis for cancer patients. However, the function of inflammasomes in tumor growth and metastasis remains unclear. The aim of this study is to examine the effect of NLRP3 inflammasome activation in regulating the progression of prostate cancer.

First, we screened the ability of NLRP3 inflammasome activation in prostate cells due to cancer heterogeneity. Prostate cell lines were treated with LPS/ATP to induce NLRP3 inflammasome activation. Our results showed that LPS/ATP significantly induced the secretion of IL-1 beta in PC3 (human prostate cancer cell line), BPH-1 (human benign prostate hyperplasia epithelial cell line) and RWPE-1 (human prostate epithelial cell line) cells. Second, we tested the effect of hypoxic condition in regulating the activation of NLRP3 inflammasome. Our results showed that hypoxia also induced the secretion of IL-1 beta in PC3, BPH-1 and RWPE-1 cells. Third, we will further examine the effect of NLRP3 inflammasome activation in regulating tumor growth and metastasis.

This study will illustrate the role of NLRP3 inflammation in modulating the progression of prostate cancer. Targeting NLRP3 inflammasome could be a strategy for prostate cancer therapy.

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