ArticleBMC cancer2021
Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Review
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- Molecular and cellular landscapes of the immune microenvironment and multiomic biomarker-sets in platinum-resistant recurrent ovarian cancers.Journal of ovarian research · 2026Review
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Advances in plasma metabolomics detection technology and its clinical applications in lung cancer and other malignancies.Holistic integrative oncology. · 2026Review
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Advances in ovarian cancer: biological insights, therapeutic innovations, and future perspectives.Journal of ovarian research · 2025Review
- Fusobacterium nucleatum-reprogrammed adipocytes promote tumor cisplatin resistance through the CCL2-CCR2 axis in the necrotic metastatic neck nodes of head and neck carcinoma.Cell communication and signaling : CCS · 2025Article
- Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells.Fundamental & clinical pharmacology · 2025Article
- Research of SLC7A11 to estimate the prognosis and immune infiltration landscape for breast cancer.Discover oncology · 2025Article
- GPT2 mediates glutamine metabolism-driven metabolic alterations in platinum-resistant ovarian cancer cells.Scientific reports · 2025Article
- LMNA R482L mutation causes impairments in C2C12 myoblasts subpopulations, alterations in metabolic reprogramming during differentiation, and oxidative stress.Scientific reports · 2025Article
- Glutamine's double-edged sword: fueling tumor growth and offering therapeutic hope.Frontiers in immunology · 2025Review
- Molecular mechanisms of cisplatin resistance in ovarian cancer.Genes & diseases · 2024Review
- Interplay between altered metabolism and DNA damage and repair in ovarian cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Stable Isotope Tracing Analysis in Cancer Research: Advancements and Challenges in Identifying Dysregulated Cancer Metabolism and Treatment Strategies.Metabolites · 2024Review
- Article
- Unveiling the mechanisms and challenges of cancer drug resistance.Cell communication and signaling : CCS · 2024Review
- Uptake and accumulation mechanisms of hexachloroplatinate(IV) ions in the unicellular alga, Pseudococcomyxa simplex.Metallomics : integrated biometal science · 2024Article
- Ovarian tumor microenvironment contributes to tumor progression and chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCisplatin (CDDP) significantly prolongs survival in various cancers, but many patients also develop resistance that results in treatment failure. Thus, this study aimed to elucidate the underlying mechanisms by which ovarian cancer cells acquire CDDP resistance.
methodsWe evaluated the metabolic profiles in CDDP-sensitive ovarian cancer A2780 cells and CDDP-resistant A2780cis cells using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). We further examined the expression of glutamine metabolism enzymes using real-time PCR and Western blot analyses. Cell viability was accessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
resultsThe results showed that levels of glutamine, glutamate, and glutathione (GSH), a key drug resistance mediator synthesized from glutamate, were significantly elevated in A2780cis cells than those in A2780 cells. Furthermore, glutamine starvation decreased the GSH levels and CDDP resistance in A2780cis cells. Interestingly, the expression of glutamine synthetase (GS/GLUL), which synthesizes glutamine from glutamate and thereby negatively regulates GSH production, was almost completely suppressed in resistant A2780cis cells. In addition, treatment of A2780cis cells with 5-aza-2'-deoxycytidine, a DNA-demethylating agent, restored GS expression and reduced CDDP resistance. In contrast, GS knockdown in CDDP-sensitive A2780 cells induced CDDP resistance.
conclusionsThe results indicate that upregulation of GSH synthesis from glutamine via DNA methylation-mediated silencing of GS causes CDDP resistance in A2780cis cells. Therefore, glutamine metabolism could be a novel therapeutic target against CDDP resistance.
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