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黄酮烷合成衍生物在不损害健康星形胶质细胞的情况下诱导脑胶质瘤癌细胞衰老。

Flavagline synthetic derivative induces senescence in glioblastoma cancer cells without being toxic to healthy astrocytes.

机构信息

INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 Rue Humann, 67000, Strasbourg, France.

Faculté de Chirurgie Dentaire, Université de Strasbourg, 67000, Strasbourg, France.

出版信息

Sci Rep. 2020 Aug 13;10(1):13750. doi: 10.1038/s41598-020-70820-6.

Abstract

Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. It is the most invasive type of glioma developed from astrocytes. Until today, Temozolomide (TMZ) is the only standard chemotherapy for patients with GBM. Even though chemotherapy extends the survival of patients, there are many undesirable side effects, and most cases show resistance to TMZ. FL3 is a synthetic flavagline which displays potent anticancer activities, and is known to inhibit cell proliferation, by provoking cell cycle arrest, and leads to apoptosis in a lot of cancer cell lines. However, the effect of FL3 in glioblastoma cancer cells has not yet been examined. Hypoxia is a major problem for patients with GBM, resulting in tumor resistance and aggressiveness. In this study, we explore the effect of FL3 in glioblastoma cells under normoxia and hypoxia conditions. Our results clearly indicate that this synthetic flavagline inhibits cell proliferation and induced senescence in glioblastoma cells cultured under both conditions. In addition, FL3 treatment had no effect on human brain astrocytes. These findings support the notion that the FL3 molecule could be used in combination with other chemotherapeutic agents or other therapies in glioblastoma treatments.

摘要

胶质母细胞瘤(GBM)是最具侵袭性的癌症之一,起源于大脑。它是由星形胶质细胞发展而来的最具侵袭性的神经胶质瘤。直到今天,替莫唑胺(TMZ)是 GBM 患者唯一的标准化疗药物。尽管化疗延长了患者的生存时间,但存在许多不良副作用,而且大多数病例对 TMZ 表现出耐药性。FL3 是一种合成的 flavagline,具有很强的抗癌活性,已知通过诱导细胞周期停滞和促进许多癌细胞系凋亡来抑制细胞增殖。然而,FL3 在胶质母细胞瘤癌细胞中的作用尚未被检测到。缺氧是 GBM 患者的一个主要问题,导致肿瘤耐药性和侵袭性增加。在这项研究中,我们探讨了 FL3 在常氧和缺氧条件下对胶质母细胞瘤细胞的影响。我们的结果清楚地表明,这种合成的 flavagline 抑制了两种条件下培养的胶质母细胞瘤细胞的增殖,并诱导了衰老。此外,FL3 处理对人脑星形胶质细胞没有影响。这些发现支持了这样一种观点,即 FL3 分子可与其他化疗药物或其他疗法联合用于胶质母细胞瘤的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a9/7426813/965ff26fb57b/41598_2020_70820_Fig1_HTML.jpg

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