Shi S, Xu J, Zhang B, Ji S, Xu W, Liu J, Jin K, Liang D, Liang C, Liu L, Liu C, Qin Y, Yu X
Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, 270 DongAn Road, Shanghai 200032, China.
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, 270 DongAn Road, Shanghai 200032, China.
Curr Mol Med. 2016;16(4):394-403. doi: 10.2174/1566524016666160316153623.
Vascular endothelial growth factor (VEGF) is highly expressed in many types of tumors, including pancreatic cancer. Tumor cellderived VEGF promotes angiogenesis and tumor progression. However, the role of VEGF in glucose metabolism remains unclear.
We investigated the role and the underlying mechanism of VEGF in the glucose metabolism of pancreatic cancer cells.
Pancreatic cancer cells were stimulated with VEGF165 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 1α (HIF1α) in pancreatic cancer tissues.
VEGF stimulation led to a metabolic transition from mitochondrial oxidative phosphorylation to glycolysis in pancreatic cancer. HIF1α 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 HIF1α expression in pancreatic tumor tissues.
VEGF enhances glycolysis in pancreatic cancer via HIF1α up-regulation. NRP1 plays a key role in VEGF-induced glycolysis.
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。肿瘤细胞衍生的VEGF促进血管生成和肿瘤进展。然而，VEGF在葡萄糖代谢中的作用仍不清楚。
我们研究了VEGF在胰腺癌细胞葡萄糖代谢中的作用及其潜在机制。
用VEGF165刺激胰腺癌细胞1或2小时。使用海马XF96细胞外通量分析仪测量氧消耗率（OCR）和细胞外酸化率（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。进行免疫组织化学（IHC）以确定胰腺癌组织中VEGF、NRP1和缺氧诱导因子1α（HIF1α）之间的相关性。
VEGF刺激导致胰腺癌中的代谢从线粒体氧化磷酸化转变为糖酵解。VEGF刺激后HIF1α和NRP1蛋白水平均升高。NRP1的下调降低了胰腺癌细胞中的糖酵解。在胰腺肿瘤组织中，NRP1和VEGF水平均与HIF1α表达相关。
VEGF通过上调HIF1α增强胰腺癌中的糖酵解。NRP1在VEGF诱导的糖酵解中起关键作用。
