Yang, Eryan; Wang, Lin; Jin, Weili; Liu, Xing; Wang, Qixue; Wu, Ye; Tan, Yanli; Wang, Yunfei; Cui, Xiaoteng; Zhao, Jixing; Tong, Fei; Hong, Biao; Xiao, Menglin; Liu, Xiaomin; Fang, Chuan; Kang, Chunsheng published the artcile< PTRF/Cavin-1 enhances chemo-resistance and promotes temozolomide efflux through extracellular vesicles in glioblastoma>, Reference of 112-63-0, the main research area is temozolomide glioblastoma chemoresistance extracellular vesicle PTRF cavin; Glioblastoma; PTRF; chloroquine; extracellular vesicles; temozolomide.
The concentration and duration of intracellular drugs have always been the key factors for determining the efficacy of the treatment. Efflux of chemotherapeutic drugs or anticancer agents is a major reason for multidrug resistance generation in cancer cells. The high expression of polymerase I and transcript release factor (PTRF) is correlated with a worse prognosis in glioma patients. However, the importance of PTRF on temozolomide (TMZ) resistance in glioblastoma (GBM) is poorly understood. TCGA data anal., CGGA data anal., transmission electron microscopy (TEM), SEM (SEM), clone formation, cell counting kit-8 (cck-8), western blot (WB), immunofluorescence (IF), immunohistochem. (IHC) and flow cytometry assays were performed to investigate the underlying mechanism and effect of PTRF on TMZ-resistance in a variety of GBM cell lines and GBM patient-derived xenograft (PDX) models. Clone formation, WB, IF, IHC and flow cytometry assays were performed to examine the efficacy of sequential therapy of TMZ followed by CQ in GBM cells and PDX models. The prognosis of GBM patients treated with TMZ was neg. correlated with PTRF expression. Our results reveal that PTRF knockdown significantly decrease proliferation and increase apoptosis in GBM after TMZ treatment. Moreover, PTRF contribute to TMZ-resistance by increasing TMZ efflux through extracellular vesicles (EVs). Furthermore, our results demonstrate that sequential therapy of TMZ followed by CQ significantly promotes the TMZ efficacy against GBM by increasing intracellular TMZ concentration ([TMZ]i). This study highlights that PTRF can act as an independent biomarker to predict the prognosis of GBM patients after TMZ treatment and describes a new mechanism contributing to TMZ-resistance. In addition, this study may provide a novel idea for GBM therapy.
Theranostics published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (Bax). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Reference of 112-63-0.
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