Induction of tumor cell apoptosis in human glioblastoma cell lines by cationic peptides

A. Lushnikova, A. V. Onyan, A. V. Kostarev, Ekaterina Yu. Rybalkina, Ksenia V Kohzikhova, S. Andreev
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Abstract

Background: Glioblastoma is very aggressive polymorphic brain tumor that is often chemo- and radio-resistant. This feature is related with glioma stem-like cells as well as with non-stem changeable cells from glioblastoma’s cell population. Search for molecular targets to overcome such resistance and to improve the effectiveness of therapy is one of the major challenges in applied molecular oncology. Objective: The aim of this study is to analyze a selective cytotoxicity of two cationic peptides (CPs) detected on two stable primary glioblastoma cell lines Glb0Sh and Glb-17. Induction of apoptosis in the cultures of recurrent glioblastoma cells and lack of cytotoxicity in normal cells was revealed by MTT assay, immunocytochemistry visualization of tumor cells after incubation with fluorescently labeled CP, RT PCR and western blotting. Results: We firstly confirm that chaperone proteins nucleolin/NCL and nucleophosmin/ NPM serve as cell molecular targets for CPs under study which has shown high selective cytotoxicity in two stable glioblastoma cell lines. These CPs are of interest for in vivo experiments as a promising anticancer agents.
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阳离子多肽诱导人胶质母细胞瘤细胞系肿瘤细胞凋亡的研究
背景:胶质母细胞瘤是一种侵袭性很强的多形性脑肿瘤,通常具有化疗和放射抵抗性。这一特征与胶质瘤干细胞样细胞以及来自胶质瘤细胞群的非干细胞变性细胞有关。寻找分子靶点来克服这种耐药性并提高治疗的有效性是应用分子肿瘤学的主要挑战之一。目的:分析两种阳离子肽(CPs)对两种稳定的原发性胶质母细胞瘤细胞系Glb0Sh和Glb-17的选择性细胞毒性。MTT法、荧光标记CP、RT - PCR和western blotting培养后肿瘤细胞的免疫细胞化学可视化显示,发现复发性胶质母细胞瘤细胞诱导凋亡,正常细胞无细胞毒性。结果:我们首次证实了伴侣蛋白nucleolin/NCL和nucleophosmin/ NPM是正在研究的CPs的细胞分子靶点,在两种稳定的胶质母细胞瘤细胞系中显示出高选择性的细胞毒性。这些CPs作为一种有前景的抗癌药物,在体内实验中具有重要意义。
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