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The Effect of Blocking Neurokinin-1 Receptor by Aprepitant on the Inflammatory and Apoptosis Pathways in Human Ovarian Cancer Cells
Cell Biochemistry and Biophysics ( IF 1.8 ) Pub Date : 2022-10-05 , DOI: 10.1007/s12013-022-01100-5
Abbas AlAlikhan 1 , Atefeh Ghahremanloo 1 , Hossein Javid 2 , Safieh Ebrahimi 1 , Seyed Isaac Hashemy 1, 3
Affiliation  

Ovarian cancer is the seventh most common cancer globally, and the second most common cancer among women with significant mortality. Toward this end, it is shown that substance P (SP) is involved in tumor initiation and progression through the neurokinin-1 receptor (NK1R). However, the exact molecular mechanism of the SP/NK1R system in ovarian cancer is not yet fully clarified. In this in vitro study, we decided to investigate the effect of the SP/NK1R system and blockage of NK1R by its specific antagonist (Aprepitant) on the proliferation of ovarian cancer cells as well as the alteration of inflammatory pathways. Our results revealed that Aprepitant stimulated apoptotic cell death and attenuated inflammation of ovarian cancer cells through the NF-kB and P53 signaling pathways. After treatment with Aprepitant, the expression of downstream anti-apoptotic genes related to the NF-kB pathway (survivine and bcl2) was decreased. However, we indicated the positive effect of SP on the proliferation of ovarian cancer cells by inducing the expression of NF-kB protein and NF-kB anti-apoptotic target genes. Moreover, Pro-apoptotic p53 target genes (P21 and Bax) were increased through aprepitant treatment, while SP attenuated these genes’ expression. Besides, ROS generation in ovarian cancer cells after treatment with SP induced, while blocking of NK1R with Aprepitant reduced the level of ROS generation. Given this, our data suggest that this NK1R might be used as an important therapeutic target in ovarian cancer and Aprepitant could be considered a new drug in ovarian cancer therapy.



中文翻译:

阿瑞匹坦阻断Neurokinin-1受体对人卵巢癌细胞炎症和凋亡通路的影响

卵巢癌是全球第七大最常见的癌症,也是女性死亡率第二高的癌症。为此,表明 P 物质 (SP) 通过神经激肽-1 受体 (NK1R) 参与肿瘤的发生和进展。然而,SP/NK1R系统在卵巢癌中的确切分子机制尚未完全阐明。在这项体外研究中,我们决定研究 SP/NK1R 系统及其特异性拮抗剂(阿瑞匹坦)对 NK1R 的阻断对卵巢癌细胞增殖以及炎症通路改变的影响。我们的研究结果表明,阿瑞匹坦通过 NF-kB 和 P53 信号通路刺激凋亡细胞死亡并减轻卵巢癌细胞的炎症。用阿瑞匹坦治疗后,与 NF-kB 通路相关的下游抗凋亡基因(survivine 和 bcl2)的表达降低。然而,我们通过诱导 NF-kB 蛋白和 NF-kB 抗凋亡靶基因的表达表明了 SP 对卵巢癌细胞增殖的积极作用。此外,通过阿瑞匹坦处理,促凋亡 p53 靶基因(P21 和 Bax)增加,而 SP 减弱了这些基因的表达。此外,用 SP 治疗后卵巢癌细胞中 ROS 的产生诱导,而用 Aprepitant 阻断 NK1R 降低了 ROS 的产生水平。鉴于此,我们的数据表明,这种 NK1R 可能被用作卵巢癌的重要治疗靶点,阿瑞匹坦可被视为卵巢癌治疗的新药。然而,我们通过诱导 NF-kB 蛋白和 NF-kB 抗凋亡靶基因的表达表明了 SP 对卵巢癌细胞增殖的积极作用。此外,通过阿瑞匹坦处理,促凋亡 p53 靶基因(P21 和 Bax)增加,而 SP 减弱了这些基因的表达。此外,用 SP 治疗后卵巢癌细胞中 ROS 的产生诱导,而用 Aprepitant 阻断 NK1R 降低了 ROS 的产生水平。鉴于此,我们的数据表明,这种 NK1R 可能被用作卵巢癌的重要治疗靶点,阿瑞匹坦可被视为卵巢癌治疗的新药。然而,我们通过诱导 NF-kB 蛋白和 NF-kB 抗凋亡靶基因的表达表明了 SP 对卵巢癌细胞增殖的积极作用。此外,通过阿瑞匹坦处理,促凋亡 p53 靶基因(P21 和 Bax)增加,而 SP 减弱了这些基因的表达。此外,用 SP 治疗后卵巢癌细胞中 ROS 的产生诱导,而用 Aprepitant 阻断 NK1R 降低了 ROS 的产生水平。鉴于此,我们的数据表明,这种 NK1R 可能被用作卵巢癌的重要治疗靶点,阿瑞匹坦可被视为卵巢癌治疗的新药。通过阿瑞匹坦处理增加了促凋亡 p53 靶基因(P21 和 Bax),而 SP 减弱了这些基因的表达。此外,用 SP 治疗后卵巢癌细胞中 ROS 的产生诱导,而用 Aprepitant 阻断 NK1R 降低了 ROS 的产生水平。鉴于此,我们的数据表明,这种 NK1R 可能被用作卵巢癌的重要治疗靶点,阿瑞匹坦可被视为卵巢癌治疗的新药。通过阿瑞匹坦处理增加了促凋亡 p53 靶基因(P21 和 Bax),而 SP 减弱了这些基因的表达。此外,用 SP 治疗后卵巢癌细胞中 ROS 的产生诱导,而用 Aprepitant 阻断 NK1R 降低了 ROS 的产生水平。鉴于此,我们的数据表明,这种 NK1R 可能被用作卵巢癌的重要治疗靶点,阿瑞匹坦可被视为卵巢癌治疗的新药。

更新日期:2022-10-05
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