Abstract
e17028 Background: Bladder cancer is one of the most common malignancies of urinary system with the forth incidence rate and the eighth leading mortality rate in male genitourinary tumors. Hypoxia environment activates the hypoxia‐signalling pathway, principally via hypoxia‐inducible transcription factors (HIF) to activate numerous target genes which mediate embryonic vascularization, metabolism, tumor angiogenesis and the other processes to supply tissues with blood and oxygen. Inflammasomes are multiprotein signal responsible for the maturation of proinflammatory cytokines IL-1β and IL-18 as well as trigger the inflammatory cell pyroptosis. Recent study showed that HIF-1α promotes NLRP3 inflammasome activation in bleomycin-induced acute lung injury. However, the role of HIF1α in regulating the progression of bladder cancer has not been examined so far. The present study aimed to investigate the effect of HIF-1α on NLRP3 inflammasome activation in urothelial carcinoma. Methods: In this research, urothelial carcinoma cell lines were treated with NLRP3 inflammasome inducers, LPS/ATP, to induce NLRP3 inflammasome activation. Results: Our preliminary results showed that both T24 and 5637 bladder cancer cells can be induced NLRP3 inflammasome activation and IL-1β secretion. In addition, hypoxia also induces the secretion of IL-1β in T24 cells. We further investigated the effect of NLRP3 inflammasome activation in modulating EMT-related protein levels, migration and invasion in bladder cancer T24 cells. Our results demonstrated that NLRP3 inflammasome activation promotes tumor growth and metastasis in bladder cancer cells. Furthermore, knockdown of HIF1α reduces both inflammatory response and migratory activity in bladder cancer. Conclusions: Collectively, these results suggest that targeting NLRP3 inflammasome might offer potential to treat hypoxic malignant tumor in bladder carcinoma.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: 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.