Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells
Open accessAbstract
OBJECTIVE: To investigate the effect of all-trans retinoic acid(ATRA) on the proliferation and differentiation of brain tumor stem cells(BTSCs) in vitro. METHODS: Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP) in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS) were observed. RESULTS: BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P < 0.01). In serum-containing medium, the expression percentages of CD133 and GFAP in the differentiated BTSCs were (2.29% +/- 0.27%) and (75.60% +/- 4.03%) respectively in the ATRA group, and (7.05% +/- 0.49%) and (12.51% +/- 0.77%) respectively in the control group. The differentiation rate of BTSCs in the ATRA group was significantly higher than that in the control group (P < 0.05), but there was still CD133 expressed in the ATRA group. The differentiated BTSCs could re-form BTSs in serum-free medium. The percentage of BTS formation in the ATRA group was(4.84% +/- 0.32%), significantly lower than that in the control group (17.71% +/- 0.78%) (P < 0.05), and the time required for BTS formation in the ATRA group was (10.07 +/- 1.03)d, significantly longer than that in the control group (4.08 +/- 0.35)d (P < 0.05). CONCLUSION: ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.
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ATRA inhibits proliferation of glioblastoma cells in vitro and in vivo, while promoting their differentiation.
“ATRA inhibits proliferation of glioblastoma cells in vitro and in vivo, while promoting their differentiation117,118.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [118]
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Self-citation
- Authors
- Niu, C. S., Li, M. W., Ni, Y. F., Chen, J. M., Mei, J. M., Li, J., & Fu, X. M.
- Affiliations
- Anhui Medical University (CN)
- Corresponding author
- Niu, Chao Shi
- Venue
- Journal of Experimental & Clinical Cancer Research
- Published
- 2010-08-17
- Volume
- 29
- Issue
- 1
- Pages
- 113-113
- ISSN
- 0392-9078 (ISSN-L)
- 1756-9966
- PMC
- PMC2931453
- OpenAlex
- W2106873042
- Cited by
- 37
- References
- 14
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (30672166)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- all-trans retinoic acid, brain tumor stem cells, glioblastoma, cell proliferation, differentiation, CD133, glial fibrillary acidic protein, serum-free medium, growth factors, tumor sphere formation, stem cell isolation, limiting dilution, clonogenic assay, MTT assay, immunofluorescence, retinoids, cancer stem cells
- MeSH terms
- AC133 Antigen, Antineoplastic Agents, Brain Neoplasms, Cell Differentiation, Glial Fibrillary Acidic Protein, Glioblastoma, Glycoproteins, Humans, Peptides, Time Factors, Tretinoin, Tumor Cells, Cultured, Neoplastic Stem Cells, Antigens, CD, Culture Media, Serum-Free, Spheroids, Cellular, Serum, Cell Proliferation
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