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

Abstract

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.

Mechanisms of reversal of temozolomide resistance in glioblastoma through downregulation of BCL3 by the Tumor Electric Field Therapy

“…Notably, several studies have demonstrated the close relationship between the extracellular matrix (ECM) and drug resistance in various cancers. Changes in the ECM structure in glioblastoma (GBM) have been shown to increase resistance to temozolomide (TMZ) treatment [29][30][31]. GBM cells can also modify the ECM by secreting hyaluronic acid, which enhances resistance to lysovirus treatment [31].…”

All‐trans retinoic acid exhibits anti‐proliferative and differentiating activity in Merkel cell carcinoma cells via retinoid pathway modulation

“…19 Strong antineoplastic and cyto-differentiating activities for ATRA have been demonstrated in myelodysplastic diseases and solid cancers such as lung, breast and prostate carcinomas as well as brain tumours. 20,21 ATRA can suppress the proliferation of primary/metastatic cells in skin neoplasms such as melanoma and inhibit tumour growth in melanoma patients, as documented in clinical trials. 22 We aimed to evaluate the impact of ATRA treatment on MCC cells.…”

“…ATRA drives tumour cell differentiation by modulating the retinoid signalling, leading to anti‐proliferative/pro‐apoptotic effects 19 . Strong antineoplastic and cyto‐differentiating activities for ATRA have been demonstrated in myelodysplastic diseases and solid cancers such as lung, breast and prostate carcinomas as well as brain tumours 20,21 . ATRA can suppress the proliferation of primary/metastatic cells in skin neoplasms such as melanoma and inhibit tumour growth in melanoma patients, as documented in clinical trials 22 …”

Retracted: Human Glioma Cells Therapy Using ATRA‐Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

“…Tis article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. Tis investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”