Carvedilol induces pyroptosis through NLRP3-caspase1-ASC inflammasome by nuclear migration of NF-κB in prostate cancer models

作者全名："Zeng, Yan; Li, Mei-xi; Wu, Shi-qi; Xu, Chen"

作者地址："[Zeng, Yan; Li, Mei-xi; Wu, Shi-qi; Xu, Chen] Chongqing Med Univ, Inst Life Sci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Xu, C (通讯作者)，Chongqing Med Univ, Inst Life Sci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：MOLECULAR BIOLOGY REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001150469600012

JCR分区：Q3

影响因子：2.6

年份：2024

卷号：51

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Carvedilol; Pyroptosis; NLRP3; NF-kappa B; Prostate cancer

摘要："Background Pyroptosis is an inflammatory type of programmed cell death, and could overcome the drug-resistance induced by anti-apoptotic effect of cancers. Carvedilol (CVL), a beta-adrenergic receptors antagonist, has shown anti-inflammatory response and anti-cancer effect. The aim of this study is to investigate whether pyroptosis can be activated by CVL in prostate cancer (PCa). Methods and results Datasets were used to analyze the expressions of pyroptosis-related proteins. Intracellular morphological change, cell viability, LDH and Il-1 beta release by cells,, and Hoechst/PI staining were used to detect the occurrence of pyroptosis. Realtime-PCR, western blot, immunofluorescence, and immunohistochemistry (IHC) were used to investigate the expressions of pyroptosis-related proteins. Datasets analyze showed the expressions of NLRP3, Caspase 1, ASC and GSDMD were all decreased in PCa comparing with normal tissues, but without prognostic significance. CVL treatment weakened the viabilities of PCa cells. Cell morphology changing, cytoplasmic vacuole formation, membrane integrity loss, LDH and IL-1 beta release and PI positive cells increasing were observed. NLRP3, Caspase 1, ASC, GSDMD and N-GSDMD expressions were elevated after CVL treatment, accompanied by a tendency of NF-kappa B transferring into nucleus. In vivo, CVL inhibited the growth of subcutaneous transplanted tumor. IHC showed CVL increased the expressions of NLRP3, ASC, and GSDMD, and decreased the expression of Ki-67 in transplanted tumor tissues. Conclusion This study demonstrated that CVL could induce pyroptosis in PCa cells through NLRP3-caspase1-ASC inflammasome by promoting nuclear translocation of NF-kappa B, which would lay a foundation for the application of adrenergic receptor antagonist in PCa."

基金机构：National Natural Science Foundation of China

基金资助正文：No Statement Available