研究动态
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前列腺癌 SP/NK1R 系统的体外促炎性作用:着眼于核因子-κB (NF-κB) 及其促炎靶基因。

The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes.

发表日期:2023 Apr 24
作者: Safieh Ebrahimi, Bahareh Erfani, Abbas Alalikhan, Hamidreza Ghorbani, Mahdi Farzadnia, Amir R Afshari, BaratAli Mashkani, Seyed Isaac Hashemy
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

前列腺癌是男性的主要全球健康威胁之一,与慢性炎症密切相关。神经肽物质P(SP)通过神经激肽受体(NK-1R)发挥作用,诱导多种促炎作用,这些作用强烈涉及数种疾病(包括癌症)的发病。因此,我们旨在研究SP / NK1R复合物在前列腺癌中的促炎功能及其抑制剂aprepitant 对其的治疗作用。我们使用MTT酶促分析法以评估前列腺癌细胞中aprepitant的细胞毒性。我们通过Western blot法评估蛋白质表达水平。应用定量实时PCR(qRT-PCR)测量促炎性细胞因子的mRNA表达水平。同时,使用酶联免疫吸附法分析促炎性细胞因子的蛋白质浓度。我们观察到SP提高了促炎性细胞因子(IL-1β、IL-6和TNF-α)的水平,而aprepitant的处理减少了SP的效果。我们还指出,SP增加了核因子-kappa B(NF-κB)的蛋白水平,作为炎症过程的主要调节因子,并且是一个NF-κB靶基因,在前列腺癌细胞中同时增加了环氧合酶2(COX-2)的蛋白质水平,而aprepitant的处理则逆转了这些效应。总之,我们的发现强调了SP / NK1R系统在前列腺癌细胞中调节促炎反应的重要性,并提出了aprepitant可作为治疗癌症相关炎症的新型抗炎药物的开发建议。© 2023年作者授予Springer Science+Business Media、LLC、Springer Nature的独家许可。
Prostate cancer is one of the main global health threats for men which is in close association with chronic inflammation. Neuropeptide substance P (SP), acting through neurokinin receptor (NK-1R), induces various pro-inflammatory responses which are strongly involved in the pathogenesis of several diseases as well as cancer. Therefore, we aimed to investigate the pro-inflammatory functions of the SP/NK1R complex in prostate cancer and the therapeutic effects of its inhibition by NK-1R antagonist, aprepitant, in vitro. MTT assay was conducted for the cytotoxicity assessment of aprepitant in prostate cancer cells. The protein expression levels were evaluated by Western blot assay. Quantitative real-time PCR (qRT-PCR) was applied to measure mRNA expression levels of pro-inflammatory cytokines. Concurrently, the protein concentrations of pro-inflammatory cytokines were also analyzed by enzyme-linked immunosorbent assay. We observed that SP increased the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), while treatment with aprepitant reduced the effects of SP. We also indicated that SP increased the protein levels of nuclear factor-kappa B (NF-κB), as the main regulator of inflammatory processes, and also an NF-κB target gene, cyclooxygenase 2 (COX-2) in prostate cancer cells, while treatment with aprepitant reversed these effects. Taken together, our findings highlight the importance of the SP/NK1R system in the modulation of pro-inflammatory responses in prostate cancer cells and suggest that aprepitant may be developed as a novel anti-inflammatory agent for the management of cancer-associated inflammation.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.