Targeting Glutamine Metabolism through Glutaminase Inhibition Suppresses Cell Proliferation and Progression in Nasopharyngeal Carcinoma


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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 in vivo experiments of subcutaneous tumor formation in mice and in vitro 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) via PI3K/AKT/mTOR pathway in NPC in vitro and in vivo. 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.

Sobre autores

Chang Su

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital,, Southern Medical University

Autor responsável pela correspondência
Email: info@benthamscience.net

Minghan Li

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University

Email: info@benthamscience.net

Yuxin Yang

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical Universit

Email: info@benthamscience.net

Ziying Wang

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University

Email: info@benthamscience.net

Qianru Wang

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University

Email: info@benthamscience.net

Weijia Wang

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University

Email: info@benthamscience.net

Xuemin Ma

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital,, Southern Medical University

Email: info@benthamscience.net

Rongrong Jie

Department of Health Management, Nanfang Hospital, Southern Medical University

Email: info@benthamscience.net

Huaihong Chen

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University,

Autor responsável pela correspondência
Email: info@benthamscience.net

Xiangping Li

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University

Autor responsável pela correspondência
Email: info@benthamscience.net

Juan Lu

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital,, Southern Medical University

Autor responsável pela correspondência
Email: info@benthamscience.net

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