The basic approach to target vascular endothelial growth factor (VEGF) expression in liver cancer under hypoxic condition.

尽管血管内皮生长因子(VEGF)在高血管肿瘤的生长中起作用，但旁分泌调节其受体在血管内皮细胞上表达的机制尚不清楚。本研究旨在研究低氧暴露的HepG2细胞释放的血管内皮生长因子是否会改变两种不同的受体KDR和FIT-1，*n的表达。分别在20%02和1%02中培养16h，检测VEGFm RNA及其蛋白的表达。将HepG2细胞条件培养液(CM)作用于人脐静脉内皮细胞(HUVECs)，RT-PCR法检测VEGE受体的mRNA表达。低氧刺激后，HepG2细胞上调VEGE的表达和VEGE的释放，缺氧CM优先刺激HUVECs表达FIT-1，而不是KOR。…反义寡核苷酸阻断低氧暴露人肝癌细胞血管内皮生长因子的释放此外，缺氧-CM诱导的内皮细胞Fit-1基因表达上调仍可维持。这些结果表明，低氧暴露的肝癌细胞不仅可以产生血管内皮生长因子，而且可以通过血管非依赖性机制旁分泌诱导FIT-1。经导管肝动脉栓塞术(TAE)是肝细胞癌(HGC)的低氧挑战之一。因此，我们检测了在治疗过程中接受TAE治疗的肝细胞癌患者的血清VEGE水平。方法：研究方法。对38例肝细胞癌合并丙型肝炎病毒阳性的肝硬变患者进行了研究。在TAE前及TAE后第1、3、7天在知情同意的情况下采集外周血。检测血清血管内皮生长因子和肝细胞生长因子(HGF)水平。测定血清支链氨基酸(BCAA)与酪氨酸(Tyr)的摩尔比(BTR)及血清AST、ALT、LDH水平。结果。虽然AST、ALT、LDH在TAE后1天内达到峰值，但7天后仍显著升高。尽管肝细胞生长因子水平与血管内皮细胞生长因子水平呈显著正相关，但血管内皮细胞瘤栓塞术后两者无明显相关性，提示血管内皮生长因子的分泌可能与临床低氧干预、血管内皮细胞生长因子及氨基酸代谢状态无关。血管内皮生长因子可作为肝肿瘤缺血的敏感标志物。较少

Although vascular endothelial growth factor (VEGF) plays a role in growth of hypervascular tumors, mechanisms for paracrine regulation of its receptor expression on vascular endothelial cells remain unknown. This study aimed to investigate whether VEGF released from hypoxia-exposed HepG2 cells alter expression of two distinct receptors, KDR and fit-1, *n human umbilical venous endothelial cells (HUVECs). HepG2 cells Were cultured in 20% 02 or 1% 02 for 16 hours in order to examine induction of VEGF mRNA and its protein expression. Conditioned media of HepG2 cells (CM) were applied to HUVECs under normoxic conditions, and expression of mRNA for the VEGE receptors was determined by RT-PCR.In response to the hypoxic challenge, HepG2 cells upregulated VEGF mRNA and the release of VEGE.The hypoxia-CM stimulated preferentially the mRNA expression of fit-1, but not that of KOR in HUVECs. When the VEGF release from hypoxia-exposed HepG2 cells was blocked by its antisense-oligodeoxynucleotide, … More the endothelial fit-1 mRNA upregulation elicited by the hypoxia-CM was still maintained. These results suggest that hypoxia-exposed hepatic cancer cells can not only produce VEGF but also evolve paracrine induction of fit-1 through VEGE-independent mechanisms.Transcatheter hepatic arterial embolization (TAE) therapy is one of the hypoxic challenge to hepatocellular carcinoma (HGC). Therefore, we examined the level of VEGE in sera of patients with HCC who underwent TAE during the course of the treatment. Methods. Thirty eight patients with HCC and hepatitis C virus-positive cirrhosis were studied. Peripheral blood samples were taken before and 1, 3 7 days after TAE with informed consent. The serum levels of VEGF as well as hepatocyte growth factor (HGF), another hepatic remodeling factor, were measured. The molar ratio (BTR) of serum branched chain amino acid (BCAA) to tyrosine (Tyr), the serum levels of AST, ALT and LDH were also examined. Results. Although the level of AST, ALT and LDH *ched to the peak value within 1 day after TAE, VEGF increased significantly 7 days later. On the other hand, there were no significant alterations in the levels of HGF and BTR during the course of TAE.Although the level of HGF was significantly correlated with the level of VEGF before TAE, no remarkable correlation was observed after TAE.These data collectively suggest that VEGF may be secreted in response to clinical hypoxic intervention, TAE, independent of HGF or the condition of amino acid metabolism. VEGF may play a role as a sensitive marker for hepatic tumor ischemia. Less