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Azathioprine Antagonizes Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153908 | GEO | 2021/02/16

REPOSITORIES: GEO

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Azathioprine antagonizes aberrantly elevated lipid metabolism and induces apoptosis in glioblastoma.

Project description:Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with poor survival rate. Temozolomide (TMZ) is used as standard chemotherapy to treat GBM, but a large number of patients either respond poorly and/or develop resistance after long-term use, emphasizing the need to develop potent drugs with novel mechanisms of action. Here, using high-throughput compound screening (HTS), we found that azathioprine, an immunosuppressant, is a promising therapeutic agent to treat TMZ-resistant GBM. Through integrative genome-wide analysis and global proteomic analysis, we found that elevated lipid metabolism likely due to hyperactive EGFR/AKT/SREBP-1 signaling was inhibited by azathioprine. Azathioprine also promoted ER stress-induced apoptosis. Analysis of orthotopic xenograft models injected with patient-derived GBM cells revealed reduced tumor volume and increased apoptosis after azathioprine and TMZ co-treatment. These data indicate that azathioprine could be a powerful therapeutic option for TMZ-resistant GBM patients.

| S-EPMC7957120 | biostudies-literature

Azathioprine Antagonizes Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma

Project description:Azathioprine Antagonizes Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma

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Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [WES]

Project description:Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with poor survival rate and temozolomide (TMZ) has been used as the standard chemotherapy for GBM treatment. However, a large number of patients either respond poorly to TMZ and/or develop resistance after long-term use, urging the need for the development of potent drugs with novel mechanisms of action. Here, using high-throughput compound screening (HTS), we found azathioprine, an immunosuppressive medication, to be a promising therapeutic agent for TMZ-resistant GBM treatment. Through integrative genome-wide analysis and global proteomic analysis, we identified the elevated lipid metabolism due to hyperactive EGFR/AKT/SREBP-1 signaling pathway being inhibited by azathioprine. In addition, azathioprine causes ER stress-induced apoptosis. Orthotopic xenograft models injected with patient-derived GBM cells exhibits reduced tumor volumes and increased apoptosis by azathioprine. These overall data indicate that azathioprine could be a powerful therapeutic option for TMZ-resistant GBM patients.

2021-02-16 | GSE153680 | GEO

Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [microarray]

Project description:Expression profiling of 559T(proneural subtype of glioblastoma), 592T(mesenchymal subtype of glioblastoma) and normal human astrocyte (NHA) Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with poor survival rate and temozolomide (TMZ) has been used as the standard chemotherapy for GBM treatment. However, a large number of patients either respond poorly to TMZ and/or develop resistance after long-term use, urging the need for the development of potent drugs with novel mechanisms of action. Here, using high-throughput compound screening (HTS), we found azathioprine, an immunosuppressive medication, to be a promising therapeutic agent for TMZ-resistant GBM treatment. Through integrative genome-wide analysis and global proteomic analysis, we identified the elevated lipid metabolism due to hyperactive EGFR/AKT/SREBP-1 signaling pathway being inhibited by azathioprine. In addition, azathioprine causes ER stress-induced apoptosis. Orthotopic xenograft models injected with patient-derived GBM cells exhibits reduced tumor volumes and increased apoptosis by azathioprine. These overall data indicate that azathioprine could be a powerful therapeutic option for TMZ-resistant GBM patients.

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Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [RNA-Seq]

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Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [WES]

Project description:Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [WES]

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Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [microarray]

Project description:Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [microarray]

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Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [RNA-Seq]

Project description:Azathioprine Blocks the Aberrantly Elevated Lipid Metabolism and Induces Apoptosis in Glioblastoma [RNA-Seq]

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