神经激肽-1 受体拮抗剂和索拉非尼联合疗法是治疗肝细胞癌的有效方法

IF 0.8 Q4 GASTROENTEROLOGY & HEPATOLOGY
Heba E. Sedky, Yasmine N. Elwany, Eman S. El Alfy, Mona N. Elwany, Yasmin M. Nabil, Hazem F. Manna, Mohamed A. Abdelaziz, Wessam F. El Hadidy
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引用次数: 0

摘要

肝细胞癌(HCC)是肝脏中最常见的原发性恶性肿瘤。口服多激酶抑制剂索拉非尼(Sorafenib)等治疗无法治愈的 HCC 的药物副作用大,疗效也值得怀疑。神经激肽-1 受体(NK1R)在炎症和肿瘤环境中发挥着重要作用,包括抵抗细胞死亡、诱导血管生成以及促进细胞迁移和增殖。此外,NK-1R 在包括 HCC 在内的人类肿瘤细胞中过度表达。此外,NK-1R 拮抗剂之一 Aprepitant 在体内和体外具有多种抗肿瘤活性(抗增殖、凋亡、抗迁移和抗血管生成)。分析索拉非尼与阿瑞匹坦联合治疗 HCC 的有效性(实验)。在这项回顾性实验研究中,人类 HCC 细胞系 HepG2 细胞分别暴露于浓度不断增加的索拉非尼单药、阿培南单药以及索拉非尼和阿培南联合用药,对细胞毒性、细胞凋亡、MMP-9、血管内皮生长因子、NF-kB p-65、p-AKT 和 p-ERK 进行了评估。此外,还对 50 块埃及 HCC 患者的 HCC 石蜡切片和另外 50 块仅作为对照的肝硬化石蜡切片进行了免疫细胞化学分析,以评估 NK-1 受体的表达程度。与单用索拉非尼和单用阿瑞匹坦相比,联合疗法的 MMP-9、血管内皮生长因子、NF-kB p-65、p-AKT 和 p-ERK 水平下降幅度更大。此外,联合治疗组的细胞凋亡率和细胞毒性明显高于单药治疗组,并具有更强的抗炎、抗血管生成和抗转移作用。此外,在50个HCC石蜡块中,大多数(60%)显示出较强的NK-1表达;在应用多变量分析时,这与患者的无进展生存期(PFS)显著相关(P < 0.05),但与总生存期(OS)无关。因此,阿普瑞坦和索拉非尼联合治疗HCC可能是一种很有前景的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combined neurokinin-1 receptor antagonist and sorafenib is a promising approach for hepatocellular carcinoma therapy
HCC (Hepatocellular carcinoma) is the most common primary malignant cancer in the liver. Treatment options to incurable HCC such as sorafenib, an oral multikinase inhibitor, had numerous side effects and questionable effectiveness. Neurokinin-1 receptor (NK1R) have a major role in inflammation and tumour environment including the resistance to cell death, the induction of angiogenesis and the promotion of cell migration and proliferation. Additionally, NK-1R is over-expressed in human tumour cells including HCC. Moreover, Aprepitant, one of the NK-1R antagonists exerts multiple antitumor activities (antiproliferative, apoptotic, antimigration, and antiangiogenesis) in vivo and in vitro. To analyze the effectiveness of combining sorafenib with aprepitant in the management of HCC (experimental). In this retrospective experimental study, the human HCC cell line, HepG2, cells were exposed to increasing concentrations of sorafenib alone, aprepitant alone and combination of both sorafenib and aprepitant evaluation of cytotoxicity, apoptosis, MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK were done. Moreover, The extent of the NK-1 receptor expression was assessed by immunocytochemistry on 50 HCC paraffin blocks of Egyptian HCC patients and another 50 paraffin blocks of liver cirrhosis only as a control. Decreased levels of MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK was more substantial in the combination therapy compared to sorafenib alone and aprepitant alone. Moreover, the rate of apoptosis and cytotoxicity were significantly higher in the combination treatment group than the monotherapy groups with more anti inflammatory, anti angiogentic and anti metastatic effects. Also, among the 50 HCC paraffin blocks, the majority (60%) showed a strong NK-1 expression; which significantly (p < 0.05) correlated with the progression free survival (PFS) but not the overall survival (OS) of the patients when applying multivariate analysis. HCC had strong expression and immunostaining for NK1R.Therefore, combined aprepitant and sorafenib may be a promising approach in HCC treatment compared to each one alone.
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来源期刊
Egyptian Liver Journal
Egyptian Liver Journal Medicine-Hepatology
CiteScore
1.60
自引率
0.00%
发文量
60
审稿时长
9 weeks
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