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2000
Volume 23, Issue 17
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background: Glutaminase (GLS), the key enzyme involved in glutamine metabolism, has been identified as a critical player in tumor growth and progression. The GLS inhibitor CB-839 has entered several clinical trials against a variety of tumors. Objective: Our study aimed to investigate the role and underlying mechanism of GLS and its inhibitor CB-839 in nasopharyngeal carcinoma (NPC). Methods: The expression, downstream genes, and signaling pathways of GLS in NPC were determined by real-time polymerase chain reaction (RT-PCR), PCR array, western blotting (WB), and immunohistochemical staining (IHC), and the phenotype of GLS was confirmed by experiments of subcutaneous tumor formation in mice and experiments of functional biology, including Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell migration, and Boyden invasion assay. Finally, it was also verified whether the treatment of NPC cells by GLS inhibitor CB-839 can change various biological functions and protein expression to achieve the purpose of blocking tumor progression. Results: GLS was remarkably overexpressed in NPC cells and tissues, predicting a poor overall survival of NPC patients. GLS promoted cell cycle, proliferation, colony formation, migratory, and invasive capacities by regulating Cyclin D2 (CCND2) PI3K/AKT/mTOR pathway in NPC and . Notably, CB-839 showed an effective anti-NPC tumor effect by blocking the biological functions of the tumor. Conclusion: The first innovative proof is that GLS promotes cell proliferation by regulating CCND2 via PI3K/AKT/mTOR pathway in NPC, and GLS inhibitor CB-839 may serve as a new potential therapeutic target for NPC treatment.

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/content/journals/acamc/10.2174/1871520623666230727104825
2023-10-01
2025-03-15
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/content/journals/acamc/10.2174/1871520623666230727104825
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  • Article Type:
    Research Article
Keyword(s): CB-839; CCND2; GLS; nasopharyngeal carcinoma; PI3K/AKT/mTOR pathway; proliferation
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