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SP/NK1R对胶质母细胞瘤癌细胞中过氧化氢酶和超氧化物歧化酶表达及活性的影响

The Effect of SP/NK1R on the Expression and Activity of Catalase and Superoxide Dismutase in Glioblastoma Cancer Cells.

作者信息

Korfi Faranak, Javid Hossein, Assaran Darban Reza, Hashemy Seyed Isaac

机构信息

Department of Biology, Faculty of Sciences, Islamic Azad University of Mashhad, Mashhad, Iran.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Biochem Res Int. 2021 Apr 21;2021:6620708. doi: 10.1155/2021/6620708. eCollection 2021.

Abstract

INTRODUCTION

Glioblastoma is the most malignant brain tumor with different therapeutic protocols, including surgery, radiotherapy, and chemotherapy. Substance P (SP), a peptide released by sensory nerves, increases cellular excitability by activating the neurokinin-1 receptor (NK1R) in several human tumor cells. Aprepitant is a potent and long-lasting NK1R antagonist, considered a new agent for inhibiting proliferation and induction of apoptosis in malignant cells. This study aimed to evaluate the effects of the SP/NK1R system on the expression and activity of catalase and superoxide dismutase (SOD) in the glioblastoma U87 cancer cell line.

METHODS

Cytotoxicity was measured by the resazurin test, 24 hours after treatment, with increasing aprepitant concentrations. The production of reactive oxygen species (ROS) was also measured 24 hours after treatment with SP and aprepitant. Enzymes activity of catalase and SOD was measured using the corresponding assay kits. Real-time PCR also measured their expression.

RESULTS

Aprepitant significantly reduced the viability of U87 cells in a concentration-dependent manner. ROS production was significantly reduced, and the activity of catalase and SOD increased after treatment with aprepitant. The expression of catalase and SOD enzymes also increased significantly in the presence of aprepitant.

CONCLUSION

The present study showed that aprepitant inhibited SP's oxidizing effects via inducing the antioxidant effects of catalase and SOD in the U87 cell line. Therefore, this drug might be introduced as a potential candidate for controlling glioblastoma cancer in animal models and clinical trials.

摘要

引言

胶质母细胞瘤是最恶性的脑肿瘤,有不同的治疗方案,包括手术、放疗和化疗。P物质(SP)是一种由感觉神经释放的肽,通过激活几种人类肿瘤细胞中的神经激肽-1受体(NK1R)来增加细胞兴奋性。阿瑞匹坦是一种强效且长效的NK1R拮抗剂,被认为是抑制恶性细胞增殖和诱导其凋亡的新型药物。本研究旨在评估SP/NK1R系统对胶质母细胞瘤U87癌细胞系中过氧化氢酶和超氧化物歧化酶(SOD)表达及活性的影响。

方法

用递增浓度的阿瑞匹坦处理24小时后,通过刃天青试验测定细胞毒性。在用SP和阿瑞匹坦处理24小时后,也测定活性氧(ROS)的产生。使用相应的检测试剂盒测定过氧化氢酶和SOD的酶活性。实时PCR也测定它们的表达。

结果

阿瑞匹坦以浓度依赖的方式显著降低U87细胞的活力。在用阿瑞匹坦处理后,ROS的产生显著减少,过氧化氢酶和SOD的活性增加。在有阿瑞匹坦存在的情况下,过氧化氢酶和SOD酶的表达也显著增加。

结论

本研究表明,阿瑞匹坦通过诱导U87细胞系中过氧化氢酶和SOD的抗氧化作用来抑制SP的氧化作用。因此,这种药物可能作为控制动物模型和临床试验中胶质母细胞瘤的潜在候选药物被引入。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f7/8084669/c237efe6b321/bri2021-6620708.001.jpg

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