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吉非替尼与替莫唑胺对U87MG胶质母细胞瘤血管生成的协同作用

Synergistic Effect of Gefitinib and Temozolomide on U87MG Glioblastoma Angiogenesis.

作者信息

Karami Afshin, Hossienpour Maryam, Mohammadi Noori Ehsan, Rahpyma Mehdi, Najafi Khadijeh, Kiani Amir

机构信息

Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Nutr Cancer. 2022;74(4):1299-1307. doi: 10.1080/01635581.2021.1952441. Epub 2021 Jul 23.

Abstract

One of the most common and deadly brain tumors is Glioblastoma multiforme (GBM). Due to recent advances in angiogenesis and its related key factors, this process as a hallmark in glioblastoma has attracted more consideration from the research community. Temozolomide (TMZ) as the first-line treatment used to treat GBM but, resistance to TMZ limits its effectiveness and the need for better treatments is still felt. Therefore, we aimed to examine the Synergistic effects of Gefitinib (GFI) in combination with Temozolomide on VEGF and MMPs in glioma cell line (U87MG). Our results displayed that GFI could induce cytotoxic effects in U87MG with IC50 values of 11 μM. U87MG cells produced large amounts of VEGF without any stimuli, and the results showed that GFI in combination with TMZ caused a significant decrease in VEGF production in these cells. In this study, we demonstrated that after treating with TMZ and GFI, there was more decrease in the levels of MMP 2 and 9 secretions in cells than treatment with GFI and TMZ doses alone. This study indicates synergistic effects of GFI plus TMZ against glioma are mediated by the potentiated anti-angiogenesis. Therefore, it can be considered as a promising plan for future studies.

摘要

多形性胶质母细胞瘤(GBM)是最常见且致命的脑肿瘤之一。由于血管生成及其相关关键因子方面的最新进展,这一作为胶质母细胞瘤标志的过程已引起研究界更多关注。替莫唑胺(TMZ)作为治疗GBM的一线药物,但对TMZ的耐药性限制了其疗效,人们仍感到需要更好的治疗方法。因此,我们旨在研究吉非替尼(GFI)与替莫唑胺联合使用对胶质瘤细胞系(U87MG)中血管内皮生长因子(VEGF)和基质金属蛋白酶(MMPs)的协同作用。我们的结果显示,GFI可在U87MG细胞中诱导细胞毒性作用,IC50值为11μM。U87MG细胞在无任何刺激的情况下会大量产生VEGF,结果表明,GFI与TMZ联合使用可使这些细胞中的VEGF产生量显著降低。在本研究中,我们证明,与单独使用GFI和TMZ剂量相比,用TMZ和GFI处理后,细胞中MMP 2和9的分泌水平下降得更多。本研究表明,GFI加TMZ对胶质瘤的协同作用是由增强的抗血管生成作用介导的。因此,它可被视为未来研究的一个有前景的方案。

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