COX‑2 inhibition in the endothelium induces glucose metabolism normalization and impairs tumor progression

内皮细胞中 COX-2 的抑制可诱导葡萄糖代谢正常化并阻碍肿瘤进展

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作者:Longhui Zhang, Sufen Li, Lan Li, Zhengqiong Chen, Ying Yang

Abstract

Previous antitumor angiogenesis strategies have focused on targeting angiogenic signals. Encouragingly, the metabolism of tumor endothelial cells (TECs) has gained attention as a therapeutic target in recent years. There is consensus that, in terms of antitumor angiogenesis, the promotion of tumor vascular regression and normalization of the remaining blood vessels are equally important. Presently, tumor vessel normalization (TVN) is an emerging antitumor treatment. The present study focused on the normalization of TEC metabolism. The results demonstrated that TECs have a hyperglycolytic metabolism. Parixibox, a cyclooxygenase‑2 (COX‑2) blocker, successively reduces the expression of vascular endothelial growth factor (VEGF) in the tumor microenvironment. VEGF further influences the expression of 6‑Phosphofructo-2-Kinase/Fructose-2,6‑Biphosphatase 3, a key glycolysis gene. Pharmacological blockade of COX‑2 restored the glucose metabolism level (particularly glycolysis) in TECs, which may be an important basic process in TVN. Therefore, COX‑2, which acts on abnormal tumor vessels, is expected to become a novel target for tumor treatment.

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