Therapeutic Perspective of Temozolomide Resistance in Glioblastoma Treatment

Qin, Xia; Liu, Liqun; Li, Yang; Zhang, Pei; Han, Da; Dong, Lei

doi:10.1080/07357907.2021.1952595

Cited by 8 publications

(7 citation statements)

References 132 publications

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“…Increasing evidence has demonstrated that glioma stem-like cells are strongly correlated with the immune suppression, tumor microenvironment and therapeutic resistance of glioblastoma [ 27 ]. Several researches indicated that GSCs targeted therapy could be the efficient strategy to prevent temozolomide resistance in glioblastoma treatment [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-155-5p derived from glioma stem-like cells promotes mesenchymal transition via targeting ACOT12

et al. 2022

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Tumor-associated exosomes play essential roles in intercellular communication and the foundation of cancer microenvironment in glioma. Many mRNAs, microRNAs (miRNAs) and proteins contained in tumor-associated exosomes can be transferred to recipient cells and contribute to the progression of tumor. Nevertheless, the cellular communication between malignant cells with different heterogeneities or characteristics and resultant tumor progression are still unclear in glioma. Here, we show that exosomes released from glioma stem-like cells (GSCs) contain a significant increasing level of miR-155-5p and could be horizontally transferred to surrounding glioma cells. High expression of miR-155-5p in plasma exosomes from patients was associated with glioma diagnosis and grading. Mechanically, we found that miR-155-5p markedly reduced the expression of acetyl-CoA thioesterase 12 (ACOT12), which played as a tumor suppressor in glioma. Furthermore, mesenchymal transition was significantly promoted in glioma cells treated with GSCs-derived exosomes. In conclusion, GSCs-derived exosomal miR-155-5p play a critical role in glioma progression and facilitating tumor aggressive growth by targeting ACOT12 and promoting mesenchymal transition. Exosomal miR-155-5p is also a potential predictive biomarker for glioma, which may provoke the development of novel diagnostic and therapeutic strategies against glioma.

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Section: Discussionmentioning

confidence: 99%

Exosomal miR-155-5p derived from glioma stem-like cells promotes mesenchymal transition via targeting ACOT12

et al. 2022

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“…The treatment of brain gliomas (especially glioblastomas), however, is still not optimal 20,21 . The clinical application of the alkylating agent TMZ shows promise for the treatment of malignant gliomas; however, acquired drug resistance eventually leads to treatment failure 7 . RIP2 kinase has been shown to play a role in acquired drug resistance 17–19 .…”

Section: Discussionmentioning

confidence: 99%

“… 6 Inevitably, after a period of TMZ treatment, the treatment often fails due to development of acquired drug resistance, which is one of the major reasons for tumor progression. 7 Therefore, the prevention of TMZ resistance is of significance for treating glioma. The causes of acquired drug resistance in gliomas are complex.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance

Wang

Jiao

et al. 2022

CNS Neurosci Ther

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Aims We aimed to investigate the role of receptor‐interacting protein 2 (RIP2) in regulation of stemness of glioma cells and chemotherapy resistance. Methods Plasmid transfection was used to overexpress RIP2. Chemical inhibitors were used to inhibit RIP2 or NF‐κB activity. Cancer stemness of glioma cells was investigated by sphere formation assays, clone formation assays, and xenograft tumor formation assays. The expression of RIP2, p‐NF‐κB, IκBα, CD133, or SOX‐2 was detected by Western blotting and immunofluorescence. Apoptosis was detected by flow cytometry. Immunohistochemical staining was used to detect the expression of RIP2, CD133, and SOX‐2 in xenograft tumor tissue. The effect of the RIP2/NF‐κB pathway on temozolomide (TMZ) resistance was evaluated by xenograft tumor assay. Results Transfection with RIP2 plasmid enhanced the sphere formation capability of U251 cells, clone formation capability, and xenograft tumor formation capability. RIP2 could mediate TMZ resistance by upregulating the expression of CD133 and SOX‐2 by activating the NF‐κB pathway. Both RIP2 inhibitor GSK583 and the NF‐κB inhibitor SC75741 could reverse the resistance of U251 cells to TMZ. Conclusion RIP2 mediates TMZ resistance by regulating the maintenance of stemness in glioma cells through NF‐κB. Interventions targeting the RIP2/NF‐κB pathway may be a new strategy for TMZ‐resistant gliomas.

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“…15,16 However, clinical application of TMZ on GBM only prolongs median survival by 2.5 months, and many cases of recurrence imply TMZresistance. 17,18 The mechanisms of TMZ resistance are multiple, including aberrant DNA repair, overexpressed ABC transporters, upregulated checkpoints for cell survival, and so forth. 15 Inhibiting a part of them cannot prevent the acquisition of drug resistance.…”

mentioning

confidence: 99%

“…A typical example is the treatment of glioblastoma multiforme (GBM) by first-line chemo-drug, Temozolomide (TMZ). TMZ delivers a methyl group to purine bases of DNA resulting in DNA strand breaks and cell cycle arrest at G2/M, thus leading to cell apoptosis. , However, clinical application of TMZ on GBM only prolongs median survival by 2.5 months, and many cases of recurrence imply TMZ-resistance. , The mechanisms of TMZ resistance are multiple, including aberrant DNA repair, overexpressed ABC transporters, upregulated checkpoints for cell survival, and so forth . Inhibiting a part of them cannot prevent the acquisition of drug resistance.…”

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confidence: 99%

Circumventing Drug Resistance Pathways with a Nanoparticle-Based Photodynamic Method

et al. 2021

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Drug resistance remains the dominant impediment for cancer therapy, not only because compensatory drug resistance pathways are always activated, but also because of the crossresistance of cancer cells to unrelated therapeutics. Herein, chemodrug-sensitive cancer cells, intrinsic drug-resistant cells, and acquired resistant cells were employed to uncover their biological response to a nanoparticle-based photodynamic method in tumoral, cellular, and molecular levels. We observed that nanoparticle-based photodynamic process with high therapeutic efficiency, intracellular delivery, and tumor penetration effect resulted in the indiscriminate and significant therapeutic outcome, in contrast to the diversiform effect of first-line chemo-drug, Temozolomide (TMZ). By real-time quantitative PCR array technique, we revealed that signals in classical resistance pathways were unaffected or downregulated, and photodynamic effect initiates cell apoptosis via downstream genes. The discovery that nanoparticulate photodynamic therapy bypasses the signals in multiple resistant pathways may imply an alternative route for combating drug resistance of cancer.

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Therapeutic Perspective of Temozolomide Resistance in Glioblastoma Treatment

Cited by 8 publications

References 132 publications

Exosomal miR-155-5p derived from glioma stem-like cells promotes mesenchymal transition via targeting ACOT12

Exosomal miR-155-5p derived from glioma stem-like cells promotes mesenchymal transition via targeting ACOT12

Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance

Circumventing Drug Resistance Pathways with a Nanoparticle-Based Photodynamic Method

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