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Targeting ETHE1 inhibits tumorigenesis in vitro and in vivo by preventing aerobic glycolysis in gastric adenocarcinoma cells

  • Authors:
    • Fangfei Li
    • Xuan Du
    • Mei Han
    • Xiaoying Feng
    • Chunmeng Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 286
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    Published online on: April 10, 2025
       https://doi.org/10.3892/ol.2025.15032
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Abstract

Gastric adenocarcinoma (GAC) is a prevalent form of cancer that frequently displays abnormal metabolism characterized by increased aerobic glycolysis. Therefore, inhibition of glycolysis may exhibit therapeutic potential for the management of advanced or recurrent gastric cancer. Analysis of ethylmalonic encephalopathy protein 1 (ETHE1) expression levels in 30 pairs of cancerous and paracancerous tissues, and 50 tumor tissue sections collected from patients with GAC revealed that ETHE1 expression was upregulated in cancerous tissues compared with in paracancerous tissues. Advanced tumor stage, lymph node metastasis and Tumor‑Node‑Metastasis stage were associated with high ETHE1 expression. Knockdown of ETHE1 expression in GAC cells resulted in a significant inhibition of cell proliferation and in cell cycle arrest, accompanied by downregulated levels of cyclin D1 and cyclin‑dependent kinase 4. ETHE1 knockdown also resulted in increased apoptosis of GAC cells, and increased caspase‑3 and caspase‑9 activity. Additionally, the expression levels of proteins associated with aerobic glycolysis were downregulated following ETHE1 knockdown, which may reduce glucose consumption, lactic acid production and ATP levels. In the in vivo experiments, suppressed tumor growth and increased tumor cell apoptosis were observed in the xenograft tumor model in animals injected with ETHE1‑knockdown GAC cells. In summary, knockdown of ETHE1 inhibited aerobic glycolysis, promoted apoptosis and inhibited tumor cell proliferation in GAC cells. These results highlight ETHE1 as a promising molecular target for the treatment of GAC potentially using an adjuvant to target it, offering a novel approach in the exploration of targeted therapeutic drugs for GAC.
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Copy and paste a formatted citation
Spandidos Publications style
Li F, Du X, Han M, Feng X and Jiang C: Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells. Oncol Lett 29: 286, 2025.
APA
Li, F., Du, X., Han, M., Feng, X., & Jiang, C. (2025). Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells. Oncology Letters, 29, 286. https://doi.org/10.3892/ol.2025.15032
MLA
Li, F., Du, X., Han, M., Feng, X., Jiang, C."Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells". Oncology Letters 29.6 (2025): 286.
Chicago
Li, F., Du, X., Han, M., Feng, X., Jiang, C."Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells". Oncology Letters 29, no. 6 (2025): 286. https://doi.org/10.3892/ol.2025.15032
Copy and paste a formatted citation
x
Spandidos Publications style
Li F, Du X, Han M, Feng X and Jiang C: Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells. Oncol Lett 29: 286, 2025.
APA
Li, F., Du, X., Han, M., Feng, X., & Jiang, C. (2025). Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells. Oncology Letters, 29, 286. https://doi.org/10.3892/ol.2025.15032
MLA
Li, F., Du, X., Han, M., Feng, X., Jiang, C."Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells". Oncology Letters 29.6 (2025): 286.
Chicago
Li, F., Du, X., Han, M., Feng, X., Jiang, C."Targeting ETHE1 inhibits tumorigenesis <em>in vitro</em> and <em>in vivo</em> by preventing aerobic glycolysis in gastric adenocarcinoma cells". Oncology Letters 29, no. 6 (2025): 286. https://doi.org/10.3892/ol.2025.15032
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