Izadi Azam, Soukhtanloo Mohammad, Mirzavi Farshad, Jalili-Nik Mohammad, Sadeghi Asie
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
Evid Based Complement Alternat Med. 2023 Jul 18;2023:8618575. doi: 10.1155/2023/8618575. eCollection 2023.
The primary malignant brain tumor glioblastoma multiforme (GBM) is most commonly detected in individuals over 60 years old. The standard therapeutic approach for GBM is radiotherapy combined with temozolomide. Recently, herbal products, such as alpha-lipoic acid (ALA) and auraptene (AUR), have shown promising anticancer effects on various cancer cells and animal models. However, it is not well understood how ALA, AUR, and their combination in GBM work to combat cancer. Thus, the purpose of this study was to investigate the antimetastatic effects of the ALA-AUR combination on U87 human glioblastoma cells.
The inhibitory effects of ALA, AUR, and the ALA/AUR combination on the migration and metastasis of U87 cells were evaluated using a wound healing test and gelatin zymography. The expression levels of matrix metalloproteinase MMP-2 and MMP-9 were assessed at the transcriptional and translational levels using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively.
Our findings revealed that combination therapy reduced cell migration and metastasis, which was indicated by the reduction in MMP-2/-9 expression both at mRNA and protein levels, as well as their enzymatic activity in U87 cells.
This study demonstrated that the combination of ALA and AUR effectively inhibited the migration and metastasis of U87 cells. Thus, given their safety and favorable specifications, the combination of these drugs can be a promising candidate for GBM treatment as primary or adjuvant therapy.
原发性恶性脑肿瘤多形性胶质母细胞瘤(GBM)最常见于60岁以上的人群。GBM的标准治疗方法是放疗联合替莫唑胺。最近,诸如α-硫辛酸(ALA)和奥瑞巴替尼(AUR)等草药产品已在各种癌细胞和动物模型中显示出有前景的抗癌作用。然而,ALA、AUR及其联合用药在GBM中抗癌的具体作用机制尚不清楚。因此,本研究的目的是探讨ALA - AUR联合用药对U87人胶质母细胞瘤细胞的抗转移作用。
采用划痕愈合试验和明胶酶谱法评估ALA、AUR以及ALA/AUR联合用药对U87细胞迁移和转移的抑制作用。分别使用定量实时聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法在转录和翻译水平评估基质金属蛋白酶MMP-2和MMP-9的表达水平。
我们的研究结果显示,联合治疗减少了细胞迁移和转移,这通过U87细胞中MMP-2/-9在mRNA和蛋白质水平的表达降低以及它们的酶活性降低得以体现。
本研究表明,ALA和AUR联合用药有效抑制了U87细胞的迁移和转移。因此,鉴于它们的安全性和良好特性,这些药物的联合用药作为GBM的一线或辅助治疗可能是一种有前景的候选方案。