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美迪紫檀堿通过上调脑胶质瘤中的 BID、BAX、CASP3、CASP8 和 CYCS 来抑制增殖并引发细胞凋亡。

Medicarpin suppresses proliferation and triggeres apoptosis by upregulation of BID, BAX, CASP3, CASP8, and CYCS in glioblastoma.

机构信息

College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing, China.

College of Life Science and Technology, Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin of Xinjiang Production and Construction Corps, Tarim University, Xinjiang, China.

出版信息

Chem Biol Drug Des. 2023 Nov;102(5):1097-1109. doi: 10.1111/cbdd.14309. Epub 2023 Jul 28.

Abstract

Glioblastoma (GBM) is the most malignant brain tumor and incurable. Medicarpin (MED), a flavonoid compound from the legume family, has multiple targets and anticancer properties. However, the role of MED in GBM remains unclear. The objective of this study was to explore the effects of MED on the apoptosis of GBM and to explain the potential molecular mechanisms. We found that the IC values of U251 and U-87 MG cells treated with MED for 24 h were 271 μg/mL and 175 μg/mL, and the IC values for 48 h were 154 μg/mL and 161 μg/mL, respectively. Additionally, the cell cycle of U251 and U-87 MG cells were arrested at the G2/M phase. Furthermore, the apoptosis rate of U251 and U-87 MG cells increased from 6.26% to 18.36% and 12.46% to 31.33% for 48 h, respectively. The migration rate of U251 and U-87 MG decreased from 20% to 5% and 25% to 15% for 12 h and these of U251 and U-87 MG decreased from 50% to 28% and 60% to 25% for 24 h. MED suppressed GBM tumorigenesis, and improved survival rate of tumor-bearing mice. Taken together, MED triggered GBM apoptosis through upregulation of pro-apoptotic proteins (BID, BAX, CASP3, CASP8, and CYCS), showed strong inhibitory effects on cell proliferation and cell migration, and displayed anti-tumor activity in nude mice.

摘要

胶质母细胞瘤(GBM)是最恶性的脑肿瘤,目前无法治愈。 medicarpin(MED)是豆科植物中的一种黄酮类化合物,具有多种靶点和抗癌特性。然而,MED 在 GBM 中的作用尚不清楚。本研究旨在探讨 MED 对 GBM 细胞凋亡的影响,并解释潜在的分子机制。我们发现,MED 处理 U251 和 U-87 MG 细胞 24 小时的 IC 值分别为 271μg/mL 和 175μg/mL,48 小时的 IC 值分别为 154μg/mL 和 161μg/mL。此外,U251 和 U-87 MG 细胞的细胞周期被阻滞在 G2/M 期。此外,U251 和 U-87 MG 细胞的凋亡率分别从 48 小时的 6.26%增加到 18.36%和 12.46%增加到 31.33%。U251 和 U-87 MG 的迁移率分别从 12 小时的 20%降低到 5%和 25%降低到 15%,而 U251 和 U-87 MG 的迁移率分别从 24 小时的 50%降低到 28%和 60%降低到 25%。MED 抑制 GBM 肿瘤发生,提高荷瘤小鼠的生存率。综上所述,MED 通过上调促凋亡蛋白(BID、BAX、CASP3、CASP8 和 CYCS)诱导 GBM 细胞凋亡,对细胞增殖和细胞迁移具有强烈的抑制作用,并在裸鼠中显示出抗肿瘤活性。

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