替莫唑胺
胶质瘤
癌症研究
类有机物
脑瘤
胶质母细胞瘤
连接蛋白
医学
肿瘤科
生物
病理
缝隙连接
神经科学
细胞生物学
细胞内
作者
Jingru Che,Thomas DePalma,Hemamylammal Sivakumar,Louisa Mezache,Miranda M. Tallman,Monica Venere,Katelyn E Swindle-Reilly,Rengasayee Veeraraghavan,Aleksander Skardal
摘要
Abstract Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three‐dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM.
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