The phenomenon of multidrug resistance in glioblastomas

Chernov, Alexander N.; Alaverdian, Diana; Галимова, Е. С.; Renieri, Alessandra; Frullanti, Elisa; Meloni, Ilaria; Shamova, Olga

doi:10.1016/j.hemonc.2021.05.006

Cited by 17 publications

(16 citation statements)

References 47 publications

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“…Increasing the efflux of drugs in cancer cells, especially in glioblastoma cells is one of the most significant and well-known mechanisms for developing MDR [18,19]. ATP binding cassette (ABC) transporter family members are considered to be essential transmembrane proteins which play a significant role in MDR with respect to pumping chemotherapeutic agents from tumor cells into the extracellular space as a result of ATP cleavage [20,21].…”

Section: Upregulation Of Mdr Transportersmentioning

confidence: 99%

“…Various studies have shown that these proteins are involved in the development of resistance against chemotherapeutic agents in this type of cancer. Moreover, co-localization of both P-gp and ABCG2 proteins is observed in glioblastoma cells, which is correlated to their joint functioning as drug transporters [19]. Consequently, blocking or inactivating ABC transporters increases the concentration of anti-neoplastic drugs in a cell [23].…”

Section: Upregulation Of Mdr Transportersmentioning

confidence: 99%

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The Role of microRNAs in Multidrug Resistance of Glioblastoma

Mahinfar

Mansoori

Rostamzadeh

et al. 2022

Cancers

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Glioblastoma (GBM) is an aggressive brain tumor that develops from neuroglial stem cells and represents a highly heterogeneous group of neoplasms. These tumors are predominantly correlated with a dismal prognosis and poor quality of life. In spite of major advances in developing novel and effective therapeutic strategies for patients with glioblastoma, multidrug resistance (MDR) is considered to be the major reason for treatment failure. Several mechanisms contribute to MDR in GBM, including upregulation of MDR transporters, alterations in the metabolism of drugs, dysregulation of apoptosis, defects in DNA repair, cancer stem cells, and epithelial–mesenchymal transition. MicroRNAs (miRNAs) are a large class of endogenous RNAs that participate in various cell events, including the mechanisms causing MDR in glioblastoma. In this review, we discuss the role of miRNAs in the regulation of the underlying mechanisms in MDR glioblastoma which will open up new avenues of inquiry for the treatment of glioblastoma.

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Section: Upregulation Of Mdr Transportersmentioning

confidence: 99%

Section: Upregulation Of Mdr Transportersmentioning

confidence: 99%

The Role of microRNAs in Multidrug Resistance of Glioblastoma

Mahinfar

Mansoori

Rostamzadeh

et al. 2022

Cancers

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“…Despite significant efforts to develop new therapies, one of the key barriers in the treatment of cancers is inherent or acquired drug resistance, a characteristic of many GBMs, which significantly limits the efficacy of drug-based treatments [13]. In GBMs treated with alkylating agents such as temozolomide (TMZ, the standard of care drug used in the treatment of GBM) [14], resistance frequently results from alkylation of guanine at the O 6 position caused by the overexpression of O 6 -methylguanine methyltransferase (MGMT) [15].…”

Section: Introductionmentioning

confidence: 99%

Metal-Based Nanostructured Therapeutic Strategies for Glioblastoma Treatment—An Update

2022

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Glioblastoma (GBM) is the most commonly diagnosed and most lethal primary malignant brain tumor in adults. Standard treatments are ineffective, and despite promising results obtained in early phases of experimental clinical trials, the prognosis of GBM remains unfavorable. Therefore, there is need for exploration and development of innovative methods that aim to establish new therapies or increase the effectiveness of existing therapies. One of the most exciting new strategies enabling combinatory treatment is the usage of nanocarriers loaded with chemotherapeutics and/or other anticancer compounds. Nanocarriers exhibit unique properties in antitumor therapy, as they allow highly efficient drug transport into cells and sustained intracellular accumulation of the delivered cargo. They can be infused into and are retained by GBM tumors, and potentially can bypass the blood–brain barrier. One of the most promising and extensively studied groups of nanostructured therapeutics are metal-based nanoparticles. These theranostic nanocarriers demonstrate relatively low toxicity, thus they might be applied for both diagnosis and therapy. In this article, we provide an update on metal-based nanostructured constructs in the treatment of GBM. We focus on the interaction of metal nanoparticles with various forms of electromagnetic radiation for use in photothermal, photodynamic, magnetic hyperthermia and ionizing radiation sensitization applications.

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“…The basic reason for the low efficacy of therapy for brain tumors is the heterogeneity of cells in tumors and the selection of neoplastic clones in response to the development of drug resistance to the effects of different therapeutic modalities [ 5 ]. The reason of it is accumulation of somatic driver mutations in G2-M DNA checkpoint and different (Notch, NF-κB, Wnt/β-catenin, PI3K/Akt) signaling cascades of stem cells stimulate the development of the tumor [ 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Anticancer Effect of Cathelicidin LL-37, Protegrin PG-1, Nerve Growth Factor NGF, and Temozolomide: Impact on the Mitochondrial Metabolism, Clonogenic Potential, and Migration of Human U251 Glioma Cells

et al. 2022

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Glioblastoma (GBM) is one of the most aggressive and lethal malignancy of the central nervous system. Temozolomide is the standard of care for gliomas, frequently results in resistance to drug and tumor recurrence. Therefore, further research is required for the development of effective drugs in order to guarantee specific treatments to succeed. The aim of current study was to investigate the effects of nerve growth factor (NGF), human cathelicidin (LL-37), protegrin-1 (PG-1), and temozolomide on bioenergetic function of mitochondria, clonogenicity, and migration of human U251 glioma cells. Colony formation assay was used to test the ability of the glioma cells to form colonies in vitro. The U251 glioma cells migration was evaluated using wound-healing assay. To study the mitochondrial metabolism in glioma cells we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) using a Seahorse XF cell Mito stress test kit and Seahorse XF cell Glycolysis stress kit, respectively. We revealed that LL-37, NGF, and TMZ show strong anti-tumorigenic activity on GMB. LL-37 (4 μM), TMZ (155 μM), and NGF (7.55 × 10−3 μM) inhibited 43.9%–60.3%, 73.5%–81.3%, 66.2% the clonogenicity of glioma U251 cells for 1–2 days, respectively. LL-37 (4 μM), and NGF (7.55 × 10−3 μM) inhibited the migration of U251 glioma cells on the third and fourth days. TMZ also inhibited the migration of human glioma U251 cells over 1–3 days. In contrast, PG-1 (16 μM) stimulated the migration of U251 glioma cells on the second, fourth, and sixth days. Anti-mitogenic and anti-migration activities of NGF, LL-37, and TMZ maybe are relation to their capacity to reduce the basal OCR, ATP-synthetase, and maximal respiration of mitochondria in human glioma U251 cells. Glycolysis, glycolytic capacity and glycolytic spare in glioma U251 cells haven`t been changed under the effect of NGF, LL-37, PG-1, and TMZ in regard to control level. Thus, LL-37 and NGF inhibit migration and clonogenicity of U251 glioma cells, which may indicate that these compounds have anti-mitogenic and anti-migration effects on human glioma cells. The study of the mechanisms of these effects may contribute in the future to the use of NGF and LL-37 as therapeutic agents for gliomas.

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The phenomenon of multidrug resistance in glioblastomas

Cited by 17 publications

References 47 publications

The Role of microRNAs in Multidrug Resistance of Glioblastoma

The Role of microRNAs in Multidrug Resistance of Glioblastoma

Metal-Based Nanostructured Therapeutic Strategies for Glioblastoma Treatment—An Update

Anticancer Effect of Cathelicidin LL-37, Protegrin PG-1, Nerve Growth Factor NGF, and Temozolomide: Impact on the Mitochondrial Metabolism, Clonogenic Potential, and Migration of Human U251 Glioma Cells

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