VEGF Promotes Glycolysis in Pancreatic Cancer via HIF1α Up-Regulation
VEGF Promotes Glycolysis in Pancreatic Cancer via HIF1α Up-Regulation
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VEGF 通过上调 HIF1 α 促进胰腺癌中的糖酵解
DOI：
10.2174/1566524016666160316153623
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发表时间：
2016-01-01
影响因子：
2.5
通讯作者：
Yu, X.
中科院分区：
文献类型：
--
作者：
Shi, S.;Xu, J.;Yu, X.
背景：血管内皮生长因子（VEGF）在包括胰腺癌在内的多种肿瘤中高表达。肿瘤细胞来源的VEGF促进血管生成和肿瘤进展。目的：探讨VEGF在胰腺癌细胞糖代谢中的作用及其机制。方法：用VEGF（165）刺激胰腺癌细胞1或2h，观察VEGF（165）对胰腺癌细胞糖代谢的影响。使用Seahorse XF96胞外通量分析仪测量耗氧速率（OCR）和胞外酸化速率（ECAR）。通过定量实时PCR检测糖酵解酶。用shRNA沉默神经纤毛蛋白1（NRP1），以研究其在VEGF诱导的糖酵解中的作用。免疫组化（IHC）检测胰腺癌组织中VEGF、NRP1和缺氧诱导因子1 α（HIF 1 alpha）的表达，分析三者之间的相关性。VEGF刺激后HIF 1 α和NRP1蛋白水平均升高。NRP1的下调减少了胰腺癌细胞中的糖酵解。结论：VEGF通过上调胰腺癌组织中HIF 1 α的表达，促进糖酵解。NRP1在VEGF诱导的糖酵解中起关键作用。
Background: Vascular endothelial growth factor (VEGF) is highly expressed in many types of tumors, including pancreatic cancer. Tumor cell-derived VEGF promotes angiogenesis and tumor progression. However, the role of VEGF in glucose metabolism remains unclear.Objective: We investigated the role and the underlying mechanism of VEGF in the glucose metabolism of pancreatic cancer cells.Method: Pancreatic cancer cells were stimulated with VEGF(165) for 1 or 2 h. The oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) were measured using the Seahorse XF96 Extracellular Flux Analyzer. Glycolytic enzymes were detected by quantitative real-time PCR. Neuropilin 1 (NRP1) was silenced by shRNA in order to investigate its role in VEGF-induced glycolysis. Immunohistochemistry (IHC) was performed to identify the correlation among VEGF, NRP1 and hypoxia inducible factor 1 alpha (HIF1 alpha) in pancreatic cancer tissues.Results: VEGF stimulation led to a metabolic transition from mitochondrial oxidative phosphorylation to glycolysis in pancreatic cancer. HIF1 alpha and NRP1 protein levels were both increased after VEGF stimulation. The down-regulation of NRP1 reduced glycolysis in pancreatic cancer cells. NRP1 and VEGF levels both correlated with HIF1 alpha expression in pancreatic tumor tissues.Conclusion: VEGF enhances glycolysis in pancreatic cancer via HIF1 alpha up-regulation. NRP1 plays a key role in VEGF-induced glycolysis.