喹啉酮诱导的口腔伯基特淋巴瘤细胞S期激酶相关蛋白-2和核因子κ

Supriatno
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引用次数: 1

摘要

3,4-二氢-6-[4-3,4-二甲氧基苯甲酰基-1-哌嗪基]-2(1H)-喹啉酮(vesnarinone)是一种具有独特而复杂作用机制的新型变力药物,已知对几种人类恶性肿瘤具有抗肿瘤活性。在本研究中,评估了vesnarinone诱导的S期激酶相关蛋白2(Skp2)和核因子κB(NF-κB)作为口腔恶性伯基特淋巴瘤(Raji细胞)分子靶标的信号转导。Raji细胞与浓度为0,1.25x10-2,2.50x10-2或5.0x10-2摩尔的vesnarinone一起孵育。24小时后,用Boyden试剂盒检测趋化细胞迁移。用胱天蛋白酶-9比色法观察细胞凋亡。为了评估Skp2、NF-kB和α-微管蛋白的水平,进行了蛋白质印迹分析。Vesnarine通过下调Skp2和NF-κB来增加Raji细胞的胱天蛋白酶-9活性,从而显著抑制趋化细胞迁移并显著诱导凋亡。Vesnarine降低Skp2和NF-κB的表达,表明这些分子可能是治疗口腔恶性伯基特淋巴瘤(BL)的靶点。这项工作的结果为BL肿瘤的治疗提供了一种有前景的方法。
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S-Phase Kinase-Associated Protein-2 and Nuclear Factor-kappa Beta as Molecular Targets of Oral Burkitt’s Lymphoma Cell Induced by Quinolinone Derivate-Vesnarinone
3,4-Dihydro-6-[4-3,4-dimethoxybenzoyl-1-piperazinyl]-2(1H)-quinolinone (vesnarinone), a novel inotropic drug with unique and complex mechanisms of action, is known to show antitumor activity against several human malignancies. In the present study, vesnarinone-induced signal transduction of S-phase kinase-associated protein 2 (Skp2) and Nuclear Factor-kappa Beta (NF-κB) as molecular targets of oral malignant Burkitt’s lymphoma (Raji cells) was evaluated. Raji cells were incubated with vesnarinone at concentrations of 0, 1.25x10-2, 2.50x10-2, or 5.0x10-2 Molar. After 24 h, chemotactic cell migration was examined by a Boyden chamber kit. Apoptosis induction was observed by caspase-9 colorimetric assay. To evaluate levels of Skp2, NF-kB, and α-tubulin, Western blot analysis was performed. Vesnarinone markedly suppressed chemotactic cell migration and significantly induced apoptosis by increasing the caspase-9 activity of Raji cells through down regulation of Skp2 and NF-κB. Vesnarinone decreased the expression of Skp2 and NF-κB indicating these molecules may be targeted for the treatment of oral malignant Burkitt’s lymphoma (BL). The results of this work offer a promising therapeutic approach for BL tumors.
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来源期刊
CiteScore
1.70
自引率
0.00%
发文量
18
审稿时长
>12 weeks
期刊介绍: In recent years a breakthrough has occurred in our understanding of the molecular pathomechanisms of human diseases whereby most of our diseases are related to intra and intercellular communication disorders. The concept of signal transduction therapy has got into the front line of modern drug research, and a multidisciplinary approach is being used to identify and treat signaling disorders. The journal publishes timely in-depth reviews, research article and drug clinical trial studies in the field of signal transduction therapy. Thematic issues are also published to cover selected areas of signal transduction therapy. Coverage of the field includes genomics, proteomics, medicinal chemistry and the relevant diseases involved in signaling e.g. cancer, neurodegenerative and inflammatory diseases. Current Signal Transduction Therapy is an essential journal for all involved in drug design and discovery.
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