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Transcriptomic Profiling of 3D Glioblastoma Tumoroids for the Identification of Mechanisms Involved in Anticancer Drug Resistance.
- Source :
-
In vivo (Athens, Greece) [In Vivo] 2020 Jan-Feb; Vol. 34 (1), pp. 199-211. - Publication Year :
- 2020
-
Abstract
- Background/aim: Among various types of brain tumors, glioblastoma is the most malignant and highly aggressive brain tumor that possesses a high resistance against anticancer drugs. To understand the underlined mechanisms of tumor drug resistance, a new and more effective research approach is required. The three dimensional (3D) in vitro cell culture models could be a potential approach to study cancer features and biology, as well as screen for anti-cancer agents due to the close mimicry of the 3D tumor microenvironments.<br />Materials and Methods: With our developed 3D alginate scaffolds, Ilumina RNA-sequencing was used to transcriptomically analyze and compare the gene expression profiles between glioblastoma cells in traditional 2-dimensional (2D) monolayer and in 3D Ca-alginate scaffolds at day 14. To verify the reliability and accuracy of Illumina RNA-Sequencing data, ATP-binding cassette transporter genes were chosen for quantitative real-time polymerase chain reaction) verification.<br />Results: The results showed that 7,411 and 3,915 genes of the 3D glioblastoma were up-regulated and down-regulated, respectively, compared with the 2D-cultured glioblastoma. Furthermore, the Kyoto Encyclopaedia of Genes and Genomes pathway analysis revealed that genes related to the cell cycle and DNA replication were enriched in the group of down-regulated gene. On the other hand, the genes involved in mitogen-activated protein kinase signaling, autophagy, drug metabolism through cytochrome P450, and ATP-binding cassette transporter were found in the up-regulated gene collection.<br />Conclusion: 3D glioblastoma tumoroids might potentially serve as a powerful platform for exploring glioblastoma biology. They can also be valuable in anti-glioblastoma drug screening, as well as the identification of novel molecular targets in clinical treatment of human glioblastoma.<br /> (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Subjects :
- Brain Neoplasms drug therapy
Brain Neoplasms genetics
Brain Neoplasms pathology
Gene Expression Profiling
Glioblastoma drug therapy
Glioblastoma pathology
Humans
Signal Transduction
Spheroids, Cellular drug effects
Spheroids, Cellular pathology
Tumor Microenvironment
Antineoplastic Agents pharmacology
Biomarkers, Tumor genetics
Drug Resistance, Neoplasm genetics
Gene Expression Regulation, Neoplastic drug effects
Glioblastoma genetics
Spheroids, Cellular metabolism
Transcriptome drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1791-7549
- Volume :
- 34
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- In vivo (Athens, Greece)
- Publication Type :
- Academic Journal
- Accession number :
- 31882480
- Full Text :
- https://doi.org/10.21873/invivo.11762