Abstract
It is widely accepted that inflammation is an important risk for the development of prostate cancer (PCa). The objective of this study was designed to investigate the potential molecular mechanism of NLR family, pyrin domain-containing protein 3 (NLRP3) inflammasome in the malignant progression of PCa. The expression level of NLRP3 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization. The effects of NLRP3 in the development of PCa by applying gain- and loss-of-function assays in LNCaP and PC3 cell lines were detected by CCK-8, TUNEL, and Transwell migration assays. The underlying mechanism of NLRP3 and caspase-1 in PCa was examined by the rescue experiments, western blotting, and qRT-PCR assays. In addition, the promoting effect of NLRP3 inflammasome was performed with an animal subcutaneous tumorigenesis experiment in vivo. The upregulation of NLRP3 was confirmed in PCa tissues and cell lines. Functionally, using CCK-8, TUNEL, and Transwell migration assays, these results showed that activation of NLRP3/caspase-1 inflammasome by LPS + ATP could enhance the ability of proliferation and migration; and decrease the apoptosis of LNCaP and PC3 cell lines. Western blotting assay showed that the activation of caspase-1 would increase after the stimulation of NLRP3 inflammasome by LPS + ATP. Moreover, the overexpression of NLRP3 promoted, while the knockdown of NLRP3 inhibited the malignant progression in PCa cell lines by positively regulating caspase-1. In addition, the rescue experiments revealed the association among NLRP3 and caspase-1, which showed that the overexpression vectors/inhibitors of caspase-1 could reverse the effect of knockdown/overexpression of NLRP3 in PCa cell lines in vitro. Finally, In in vivo experiment, the suppression of NLRP3 knockdown impaired tumor growth of PCa. Collectively, these results indicated that NLRP3 inflammasome played a vital role in promoting the malignant progression of PCa via the activation of caspase-1. Together, our findings provided insight into the mechanisms of NLRP3/caspase-1 inflammasome and revealed an alternative and potential target for the clinical diagnosis and treatment of PCa.
Highlights
Prostate cancer (PCa) is one of the most common malignancies among men worldwide, with an estimated 191,930 new cases and 33,330 new deaths of PCa in the United States in 2020 [1, 2]
The data from PCa patients were complied for investigating the blotting showed that the expression level of NLRP3 and caspase-1 expression level of NLRP3 associated with the malignant progression in the treatment of LPS + adenosine triphosphate (ATP) were dramatically increased, of PCa
We compared malignant progression in PCa cell lines the tissues from HTR-PCa and non-hormone therapy refractory To explore the biological function of NLRP3 inflammasome in PCa prostate cancer
Summary
Prostate cancer (PCa) is one of the most common malignancies among men worldwide, with an estimated 191,930 new cases and 33,330 new deaths of PCa in the United States in 2020 [1, 2]. With the over-treatment of inherently benign disease and inadequate therapies for metastatic PCa, the diagnosis and treatment technology of PCa still need to be further improved [7, 8]. The early diagnosis and intervention of PCa would help to choose the best treatment options of PCa, including radical prostatectomy, hormone therapy, chemotherapy, and radiotherapy [8]. A growing body of evidence highlights the importance of chronic inflammation for malignant proliferation, migration, angiogenesis, and resistance to chemotherapy in a variety of cancers [9]. There is an urgent need to explore cancerrelated inflammation to find new treatments that are more effective and have fewer side effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
