期刊论文详细信息
Cancer Treatment and Research Communications
NVP-BEZ235 or JAKi Treatment leads to decreased survival of examined GBM and BBC cells
Neftali Vazquez1  Megan Keniry1  Victoria Cuello1  Erin Schuenzel1  Michael Persans1  Alma Lopez1  Wendy Innis-Whitehouse2 
[1] Department of Biology, University of Texas- Rio Grande Valley, 1201 W. University Dr., Edinburg, TX 78539, United States;School of Medicine, University of Texas- Rio Grande Valley, 1201 W. University Dr., Edinburg, TX 78539, United States;
关键词: GBM;    PI3K;    Stem phenotypes;    Apoptosis;   
DOI  :  
来源: DOAJ
【 摘 要 】

Cancer cells almost universally harbor constitutively active Phosphatidylinositol-3 Kinase (PI3K) Pathway activity via mutation of key signaling components and/or epigenetic mechanisms. Scores of PI3K Pathway inhibitors are currently under investigation as putative chemotherapeutics. However, feedback and stem cell mechanisms induced by PI3K Pathway inhibition can lead to reduced treatment efficacy. To address therapeutic barriers, we examined whether JAKi would reduce stem gene expression in a setting of PI3K Pathway inhibition in order to improve treatment efficacy. We targeted the PI3K Pathway with NVP-BEZ235 (dual PI3K and mTOR inhibitor) in combination with the Janus Kinase inhibitor JAKi in glioblastoma (GBM) and basal-like breast cancer (BBC) cell lines. We examined growth, gene expression, and apoptosis in cells treated with NVP-BEZ235 and/or JAKi. Growth and recovery assays showed no significant impact of dual treatment with NVP-BEZ235/JAKi compared to NVP-BEZ235 treatment alone. Gene expression and flow cytometry revealed that single and dual treatments induced apoptosis. Stem gene expression was retained in dual NVP-BEZ235/JAKi treatment samples. Future in vivo studies may give further insight into the impact of combined NVP-BEZ235/JAKi treatment in GBM and BBC.

【 授权许可】

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