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Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP
The glioma stem cells (GSCs) performed the self-renewal, proliferation, and differentiation characteristics; their drug resistance has become the main reason for glioma clinical treatment failure. All-trans retinoic acid (ATRA) is an important inducer of cell differentiation, applied in the treatmen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570852/ https://www.ncbi.nlm.nih.gov/pubmed/34745507 http://dx.doi.org/10.1155/2021/6717582 |
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author | Li, Xinning Zou, Zheng Ma, Enlong Feng, Sizhe Han, Song |
author_facet | Li, Xinning Zou, Zheng Ma, Enlong Feng, Sizhe Han, Song |
author_sort | Li, Xinning |
collection | PubMed |
description | The glioma stem cells (GSCs) performed the self-renewal, proliferation, and differentiation characteristics; their drug resistance has become the main reason for glioma clinical treatment failure. All-trans retinoic acid (ATRA) is an important inducer of cell differentiation, applied in the treatment of hematologic diseases and other solid tumors. ATRA is a fat-soluble compound, which can easily go through the blood-brain barrier. Therefore, in this study, ATRA was used to induce the differentiation of glioma cells and glioma stem cells, reducing the degree of malignancy and improving its chemotherapy resistance. Methods and Treatment. The results of IF and PCR showed that the expression of CD133 was significantly lower than those of undifferentiated cells. Furthermore, temozolomide (TMZ) and cisplatin (CDDP), the first-line drugs, were used for the treatment of GCs and GSCs. The MTT assay results showed that the effect of the combination of the two drugs was significantly stronger than that of one of them alone. Results. Moreover, the MTT assay also demonstrated that TMZ single, CDDP single, and the combination of TMZ and CDDP can inhibit the proliferation of GCs, ATRA-GCs, GSCs, and ATRA-GSCs in a dose- and time-dependent manner; and ATRA-induced differentiation could promote those drugs inhibition effect and increased the chemotherapy sensitivity. Conclusion. Therefore, we successfully purified the suspension spherical glioma stem cells. Moreover, ATRA was demonstrated to induce the differentiation of GCs and GSCs. Furthermore, ATRA-induced differentiation promotes the inhibitive effect of TMZ and CCDP treatment on the proliferation of primary human glioma cells and glioma stem cells, suggesting that ATRA could increase the chemotherapy sensitivity of TMZ and CCDP through inducing cell differentiation. The combination of TMZ and CCDP performed a synergistic role in inhibiting the proliferation of GCs and GSCs. |
format | Online Article Text |
id | pubmed-8570852 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-85708522021-11-06 Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP Li, Xinning Zou, Zheng Ma, Enlong Feng, Sizhe Han, Song J Healthc Eng Research Article The glioma stem cells (GSCs) performed the self-renewal, proliferation, and differentiation characteristics; their drug resistance has become the main reason for glioma clinical treatment failure. All-trans retinoic acid (ATRA) is an important inducer of cell differentiation, applied in the treatment of hematologic diseases and other solid tumors. ATRA is a fat-soluble compound, which can easily go through the blood-brain barrier. Therefore, in this study, ATRA was used to induce the differentiation of glioma cells and glioma stem cells, reducing the degree of malignancy and improving its chemotherapy resistance. Methods and Treatment. The results of IF and PCR showed that the expression of CD133 was significantly lower than those of undifferentiated cells. Furthermore, temozolomide (TMZ) and cisplatin (CDDP), the first-line drugs, were used for the treatment of GCs and GSCs. The MTT assay results showed that the effect of the combination of the two drugs was significantly stronger than that of one of them alone. Results. Moreover, the MTT assay also demonstrated that TMZ single, CDDP single, and the combination of TMZ and CDDP can inhibit the proliferation of GCs, ATRA-GCs, GSCs, and ATRA-GSCs in a dose- and time-dependent manner; and ATRA-induced differentiation could promote those drugs inhibition effect and increased the chemotherapy sensitivity. Conclusion. Therefore, we successfully purified the suspension spherical glioma stem cells. Moreover, ATRA was demonstrated to induce the differentiation of GCs and GSCs. Furthermore, ATRA-induced differentiation promotes the inhibitive effect of TMZ and CCDP treatment on the proliferation of primary human glioma cells and glioma stem cells, suggesting that ATRA could increase the chemotherapy sensitivity of TMZ and CCDP through inducing cell differentiation. The combination of TMZ and CCDP performed a synergistic role in inhibiting the proliferation of GCs and GSCs. Hindawi 2021-10-29 /pmc/articles/PMC8570852/ /pubmed/34745507 http://dx.doi.org/10.1155/2021/6717582 Text en Copyright © 2021 Xinning Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Xinning Zou, Zheng Ma, Enlong Feng, Sizhe Han, Song Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP |
title | Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP |
title_full | Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP |
title_fullStr | Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP |
title_full_unstemmed | Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP |
title_short | Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP |
title_sort | human glioma cells therapy using atra-induced differentiation method to promote the inhibitive effect of tmz and ccdp |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570852/ https://www.ncbi.nlm.nih.gov/pubmed/34745507 http://dx.doi.org/10.1155/2021/6717582 |
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