Inhibition of ll β-adrenergic receptor regulates necroptosis in prostate cancer cell

作者全名：Wu, Shiqi; Li, Meixi; Chen, Fangfang; Zeng, Yan; Xu, Chen

作者地址：[Wu, Shiqi; Li, Meixi; Chen, Fangfang; Zeng, Yan; Xu, Chen] Chongqing Med Univ, Inst Life Sci, 1 Med Coll Rd, Chongqing 400016, Peoples R China

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

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001246418600001

JCR分区：Q1

影响因子：3.4

年份：2024

卷号：10

期号：11

开始页：　

结束页：　

文献类型：Article

关键词：Prostate cancer; Necroptosis; beta 2AR

摘要：As the malignant tumor with the highest incidence in male, prostate cancer poses a significant threat to the reproductive health of elderly men. Our previous studies have shown that promoting necroptosis of cancer cells can effectively inhibit cancer cell proliferation. This study includes lentivirus-mediated knockdown of ll2AR which resulted in stable transfectants that exhibited an increased ability to form clones compared to that of the negative control group. In the protein and mRNA levels, necroptosis associated RIP and mixed lineage kinase domain-like (MLKL) were significantly higher in the treatment group than they were in the control group. Furthermore, cells treated with propranolol exhibited necrotic morphology as observed by transmission electron microscopy. The combination of ll2AR suppression and necroptosis inhibitors resulted in a more potent suppression of cell proliferation compared to that observed in the control and negative control groups. Additionally, it elevated in the necrosis rate as determined by flow cytometry. Immunofluorescence staining revealed enhanced RIP and MLKL expression in the shll2AR group compared to levels in the negative control group. Co-immunoprecipitation experiments detected an interaction between ll2AR and RIP. MLKL and RIPK3 levels were significantly higher in xenograft tumor sections from the sh-ll2AR group compared to levels in the sh-NC group. To conclude, our research indicates the proliferation of PC-3 and DU-145 cprostate cancer cells can be suppressed by inhibiting ll2AR, and this occurs through the RIP/MLKL-mediated pathway of necroptosis.

基金机构：National Natural Science Foundation of China [081402282]

基金资助正文：We thank the National Natural Science Foundation of China (Number 081402282) for its support.