scholarly journals Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xinning Li ◽  
Zheng Zou ◽  
Enlong Ma ◽  
Sizhe Feng ◽  
Song Han

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.

2021 ◽  
Author(s):  
Xiu-Ying He ◽  
Xiao-Ming Zhao ◽  
Qing-Jie Xia ◽  
Lei Zhou ◽  
Ting-Hua Wang

Abstract Background Glioma is the most common primary intracranial tumors. Although great achievements in the treatment have been made, the efficacy is still not satisfactory, which imposes a great burden on patients and society. Therefore, the exploration of new and effective anti-glioma drugs is urgent. Methods Human glioma cells U251 and LN229 cells were included in the study. The proliferation was detected by cell counting kit-8, plate clone formation assay, EdU incorporation assay and xCELLigence real-time cell analyzer. The cell apoptosis was evaluated by TUNEL assay and flow cytometry. The transwell assay was for assessing the migration. Moreover, Western blot was performed to detect the protein level of Epidermal growth factor receptor (EGFR). Results In present study, we found that Scutellarin(SCU) and Lidocaine suppressed the proliferation and migration, and induced the apoptosis of human glioma cells, including U251 and LN229 cells, in a dose-dependent manner. Moreover, the combination of Scutellarin and Lidocaine further restrained the proliferation and migration ability of U251 and LN229 cells, while induced their apoptosis. Mechanistically, the effect of Scutellarin and its combination with Lidocaine on glioma cells was partially associated with the downregulation of EGFR protein. Conclusions Scutellarin and Lidocaine exert a synergistic effect on suppressing the proliferation and migration and induce the apoptosis of glioma cells partly via repressing the EGFR expression.


2019 ◽  
Vol 22 (4) ◽  
pp. 493-504 ◽  
Author(s):  
Myriam Jaraíz-Rodríguez ◽  
Rocío Talaverón ◽  
Laura García-Vicente ◽  
Sara G Pelaz ◽  
Marta Domínguez-Prieto ◽  
...  

Abstract Background Malignant gliomas are the most frequent primary brain tumors and remain among the most incurable cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulate the tumor suppressor properties of this protein in in vivo glioma models. Methods TAT-Cx43266–283 a cell-penetrating peptide which mimics the effect of Cx43 on c-Src inhibition, was studied in orthotopic immunocompetent and immunosuppressed models of glioma. The effects of this peptide in brain cells were also analyzed. Results While glioma stem cell malignant features were strongly affected by TAT-Cx43266–283, these properties were not significantly modified in neurons and astrocytes. Intraperitoneally administered TAT-Cx43266–283 decreased the invasion of intracranial tumors generated by GL261 mouse glioma cells in immunocompetent mice. When human glioma stem cells were intracranially injected with TAT-Cx43266–283 into immunodeficient mice, there was reduced expression of the stemness markers nestin and Sox2 in human glioma cells at 7 days post-implantation. Consistent with the role of Sox2 as a transcription factor required for tumorigenicity, TAT-Cx43266–283 reduced the number and stemness of human glioma cells at 30 days post-implantation. Furthermore, TAT-Cx43266–283 enhanced the survival of immunocompetent mice bearing gliomas derived from murine glioma stem cells. Conclusion TAT-Cx43266–283 reduces the growth, invasion, and progression of malignant gliomas and enhances the survival of glioma-bearing mice without exerting toxicity in endogenous brain cells, which suggests that this peptide could be considered as a new clinical therapy for high-grade gliomas.


Author(s):  
Yoshihira Kimba ◽  
Tatsuya Abe ◽  
Jian Liang Wu ◽  
Ryo Inoue ◽  
Minoru Fukiki ◽  
...  

2007 ◽  
Vol 6 (1) ◽  
pp. 42 ◽  
Author(s):  
Pabbisetty Kumar ◽  
Anjali Shiras ◽  
Gowry Das ◽  
Jayashree C Jagtap ◽  
Vandna Prasad ◽  
...  

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhaohui Li ◽  
Han Wang ◽  
Jun Wei ◽  
Liang Han ◽  
Zhigang Guo

Abstract Glioma causes significant mortality across the world and the most aggressive type of brain cancer. The incidence of glioma is believed to increase in the next few decades and hence more efficient treatment strategies need to be developed for management of glioma. Herein, we examined the anticancer effects of Indirubin against a panel of human glioma cells and attempted to explore the underlying mechanisms. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that Indirubin could inhibit the growth of all the glioma cells but the lowest IC50 of 12.5 µM was observed against the U87 and U118 glioma cells. Additionally, the cytotoxic effects of Indirubin were comparatively negligible against the normal astrocytes with an IC50 of > 100 µM. Investigation of mechanism of action, revealed that Indirubin exerts growth inhibitory effects on the U87 and U118 glioma cells by autophagic and apoptotic cell death. Annexin V/PI staining assay showed that apoptotic cell percentage increased dose dependently. Apoptosis was associated with increase in Bax decrease in Bcl-2 expressions. Additionally, the expression of autophagic proteins such as LC3II, ATG12, ATG15 and Beclin 1 was also increased. Wound heal assay showed that Indirubin caused remarkable decrease in the migration of the U87 and U118 cells indicative of anti-metastatic potential of Indirubin. Taken together, these results suggest that Indirubin exerts potent anticancer effects on glioma cells and may prove essential in the management of glioma.


Molecules ◽  
2014 ◽  
Vol 19 (11) ◽  
pp. 17202-17220 ◽  
Author(s):  
Angel Recio Despaigne ◽  
Jeferson Da Silva ◽  
Pryscila da Costa ◽  
Raquel dos Santos ◽  
Heloisa Beraldo

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