Cryptotanshinone 通过抑制 NLRP3 抑制脂多糖诱导的炎症微环境中的膀胱癌细胞恶性进展。
Cryptotanshinone Inhibits Bladder Cancer Cell Malignant Progression in a Lipopolysaccharide-Induced Inflammatory Microenvironment through NLRP3 Inhibition.
发表日期:2024
作者:
Chenye Tang, Xiao Guo, Yu Li, Yongxiang Yi, Zhiling Tang, Qihui Zhang, Bairu Luo, Kean Chen, Ke Liang, Gang Li
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
膀胱癌(BC)是泌尿生殖系统最常见的恶性肿瘤之一。本研究评估了 BC 中的核苷酸结合寡聚结构域和富含亮氨酸重复序列和热蛋白结构域的蛋白 3 (NLRP3),以及隐丹参酮对脂多糖 (LPS) 诱导下的 BC 恶性行为和 NLRP3 表达变化的影响。收集62例患者的BC组织标本,进行免疫组化检测NLRP3蛋白。培养BC和正常尿路上皮细胞系用于检测NLRP3 mRNA和蛋白。然后,用 LPS 预处理 BC 细胞以模拟炎症肿瘤微环境。接下来,将这些细胞与低或高剂量的隐丹参酮一起孵育,以评估其对肿瘤细胞恶性行为的影响,并转染NLRP3 cDNA,以在体外证实NLRP3在BC细胞中的作用。NLRP3高表达与较大的肿瘤相关直径(>2cm)、肌肉侵袭和转移。 BC 细胞中的 NLRP3 mRNA 和蛋白水平高于正常尿路上皮细胞。 LPS预处理显着促进BC细胞中NLRP3和炎症细胞因子的表达,并诱导细胞活力、迁移和侵袭。然而,隐丹参酮能够减少 LPS 诱导的 NLRP3 和炎症细胞因子表达的增加以及 BC 细胞的恶性进展。使用NLRP3 cDNA过表达NLRP3进一步促进LPS刺激后BC细胞的恶性进展,并逆转隐丹参酮减少的LPS诱导的BC细胞恶性行为。NLRP3可能在BC中具有致癌活性,而隐丹参酮在BC中的体外抗肿瘤活性可能与其相关抑制 NLRP3 表达。版权所有 © 2024 Chenye Tang 等人。
Bladder cancer (BC) is one of the most common malignancies of the urogenital system. This study assessed the nucleotide-binding oligomerization domain and leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) in BC as well as the effects of cryptotanshinone on changes in BC malignant behaviors and NLRP3 expression under a lipopolysaccharide (LPS)-induced inflammatory microenvironment.BC tissue specimens from 62 patients were collected for immunohistochemical detection of NLRP3 protein. BC and normal urothelial cell lines were cultured for the detection of NLRP3 mRNA and protein. Then, BC cells were pretreated with LPS to mimic the inflammatory tumor microenvironment. Next, these cells were incubated with a low or high dose of cryptotanshinone to assess its effects on tumor cell malignant behaviors as well as transfected with NLRP3 cDNA to confirm the role of NLRP3 in BC cells in vitro.High NLRP3 expression was associated with larger tumor diameters (>2 cm), muscle invasion, and metastasis. The levels of NLRP3 mRNA and protein were greater in BC cells than in normal urothelial cells. LPS pretreatment significantly promoted NLRP3 and inflammatory cytokine expression in BC cells, and induced cell viability, migration, and invasion. However, cryptotanshinone was able to reduce the LPS-induced increase of NLRP3 and inflammatory cytokine expression as well as the BC cell malignant progression. NLRP3 overexpression using NLRP3 cDNA further promoted BC cell malignant progression after LPS stimulation and reversed cryptotanshinone-reduced LPS-induced BC cell malignant behaviors.NLRP3 might possess oncogenic activity in BC, and the antitumor activity of cryptotanshinone in BC in vitro might be related to its inhibition of NLRP3 expression.Copyright © 2024 Chenye Tang et al.