白藜芦醇通过阻遏P-蛋白和靶向AKT/PTEN信号通路来抑制胶质母细胞瘤细胞和化疗抵抗的进程。
Resveratrol inhibits glioblastoma cells and chemoresistance progression through blockade P-glycoprotein and targeting AKT/PTEN signaling pathway.
发表日期:2023 Feb 17
作者:
Yuming Zhang, Zhen Zhang, Mahdi Mousavi, Afshin Moliani, Yousefi Bahmn, Hossein Bagheri
来源:
CHEMICO-BIOLOGICAL INTERACTIONS
摘要:
恶性胶质瘤被归类为一类耗费力气的脑肿瘤,对辐射和化疗药物具有抵抗力,并具有恶劣的预后。PI3K/AKT通路的过度活化和p-糖蛋白转运体的过度表达有助于增强胶质母细胞瘤存活和化学耐药性。因此,白藜芦醇被研究作为可能在胶质瘤中具有潜在治疗作用的药物,并可能抑制PI3K通路。在本研究中,通过MTT法评估了白藜芦醇对人U87MG和多柔比星耐药型胶质母细胞瘤细胞(U87MG / DOX)存活的影响。还通过罗丹明123摄取和ELISA检测研究了白藜芦醇克服胶质母细胞瘤细胞对多柔比星的耐药性的能力。白藜芦醇以PTEN和P53-依赖的方式减少了细胞存活率,这是与抑制PI3K信号通路和激活P-糖蛋白相关的效果。我们的研究发现,作为胶质母细胞瘤细胞的生长抑制剂和化疗增敏剂,白藜芦醇在脑癌治疗中有很大的应用前景。白藜芦醇通过上调PTEN和抑制AKT和P-糖蛋白来抑制胶质母细胞瘤细胞的进展并逆转化学耐药性。利用白藜芦醇靶向PTEN可能成为化疗增敏胶质母细胞瘤的一种新疗法。版权所有© 2023 Elsevier B.V. 发布。
Malignant gliomas have been categorized as a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, and have a poor prognosis. Hyper-activation of PI3K/AKT pathway and overexpression of p-glycoprotein transporter contributes to enhanced glioblastoma survival and chemoresistance. Resveratrol which possibly inhibits PI3K pathway, has been thus investigated for a potential therapeutic role in glioma. In the present study, the effect of resveratrol on human U87MG and doxorubicin-resistant glioblastoma cells (U87MG/DOX) survival evaluated by MTT. The ability of resveratrol to overcome doxorubicin resistance in glioblastoma cells was also explored with Rhodamines 123 uptake and ELISA assays. Resveratrol reduced cell survival in a PTEN and P53-dependent manner which was an effect associated with the inhibition of PI3K signaling pathway and via the activation of P-glycoprotein. Our finding showed that resveratrol, as a glioblastoma cell growth inhibitor and chemosensitizer, could be promising if used in the treatment of brain cancer. Resveratrol inhibits the progression of glioblastoma cells and reverses chemoresistance by upregulating PTEN, and suppressing AKT and P-glycoprotein. Targeting PTEN with resveratrol may offer a novel therapeutic approach for the chemo-sensitization of glioblastoma cells.Copyright © 2023. Published by Elsevier B.V.