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与蜂毒及其成分相关的抗癌特性的分子特征在多形性胶质母细胞瘤中的表现。

Molecular characterization of the anticancer properties associated with bee venom and its components in glioblastoma multiforme.

机构信息

Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada; New Brunswick Center for Precision Medicine, 27 Providence Street, Moncton, New Brunswick, E1C 8X3, Canada.

Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada.

出版信息

Chem Biol Interact. 2021 Sep 25;347:109622. doi: 10.1016/j.cbi.2021.109622. Epub 2021 Aug 8.

DOI:10.1016/j.cbi.2021.109622
PMID:34375656
Abstract

Glioblastoma multiforme (GBM) is a frequent form of malignant glioma. Strategic therapeutic approaches to treat this type of brain tumor currently involves a combination of surgery, radiotherapy and chemotherapy. Nevertheless, survival of GBM patients remains in the 12-15 months range following diagnosis. Development of novel therapeutic approaches for this malignancy is therefore of utmost importance. Interestingly, bee venom and its components have shown promising anti-cancer activities in various types of cancer even though information pertaining to GBMs have been limited. The current work was thus undertaken to better characterize the anti-cancer properties of bee venom and its components in Hs683, T98G and U373 human glioma cells. MTT-based cell viability assays revealed IC values of 7.12, 15.35 and 7.60 μg/mL for cell lines Hs683, T98G and U373 treated with bee venom, respectively. Furthermore, melittin treatment of these cell lines resulted in IC values of 7.77, 31.53 and 12.34 μg/mL, respectively. Cell viability assessment by flow cytometry analysis confirmed signs of late apoptosis and necrosis after only 1 h of treatment with either bee venom or melittin in all three cell lines. Immunoblotting-based quantification of apoptotic markers demonstrated increased expression of Bak and Bax, while Caspsase-3 levels were significantly lower when compared to control cells. Quantification by qRT-PCR showed increased expression levels of long non-coding RNAs RP11-838N2.4 and XIST in glioma cells treated with either bee venom or melittin. Overall, this study provides preliminary insight on molecular mechanisms via which bee venom and its main components can impact viability of glioma cells and warrants further investigation of its anticancer potential in gliomas.

摘要

多形性胶质母细胞瘤(GBM)是一种常见的恶性胶质瘤。目前,治疗这种类型脑肿瘤的策略性治疗方法包括手术、放疗和化疗的结合。然而,GBM 患者的生存时间在诊断后仍维持在 12-15 个月范围内。因此,开发针对这种恶性肿瘤的新治疗方法至关重要。有趣的是,尽管有关 GBM 的信息有限,但蜂毒及其成分在各种类型的癌症中已显示出有希望的抗癌活性。因此,本研究旨在更好地研究蜂毒及其成分在 Hs683、T98G 和 U373 人神经胶质瘤细胞中的抗癌特性。MTT 细胞活力测定法显示,蜂毒液分别处理 Hs683、T98G 和 U373 细胞的 IC 值为 7.12、15.35 和 7.60μg/mL。此外,蜂毒处理这些细胞系导致的 IC 值分别为 7.77、31.53 和 12.34μg/mL。流式细胞术分析细胞活力评估显示,在用蜂毒或蜂毒肽处理所有三种细胞系仅 1 小时后,即出现晚期细胞凋亡和坏死的迹象。基于免疫印迹的凋亡标志物定量分析显示,Bak 和 Bax 的表达增加,而 Caspase-3 水平与对照细胞相比显著降低。qRT-PCR 定量显示,用蜂毒或蜂毒肽处理的神经胶质瘤细胞中长非编码 RNA RP11-838N2.4 和 XIST 的表达水平增加。总的来说,本研究初步揭示了蜂毒及其主要成分影响神经胶质瘤细胞活力的分子机制,并证明了其在神经胶质瘤中抗癌潜力值得进一步研究。

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