There is evidence to suggest that follicle-stimulating hormone （FSH） can facilitate the neovascularization of ovarian cancers by increasing vascular endothelial growth factor （VEGF） expression in cancer cells, alt...There is evidence to suggest that follicle-stimulating hormone （FSH） can facilitate the neovascularization of ovarian cancers by increasing vascular endothelial growth factor （VEGF） expression in cancer cells, although the underlying molecular mechanism of this process is not well known. Therefore, we investigated the effect of FSH on VEGF expression in the ovarian cancer cell lines SKOV-3 and ES-2. Treatment with FSH significantly increased VEGF expression in a dose- and time-dependent manner. In addition, FSH treatment enhanced the expression of survivin and hypoxlainducible factor-1 （HIF-1α）. Knockdown of survivin or HIF-1α suppressed VEGF expression, but only knockdown of survivin inhibited FSH-stimulated VEGF expression. Pretreatment with LY294002, a phosphoinositide 3-kinase （PI3K）/AKT inhibitor, neutralized the enhanced expression of survivin induced by FSH, but treatment with U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, had no such effect. We further showed that ovarian serous cystadenocarcinoma samples had much higher incidence of positive AKT and phosphorylated AKT （pAKT） protein staining than did benign ovarian cystadenoma samples （p 〈 0.01）. The 5-year survival rate was only about 15% in patients with ovarian serous cystadenocarcinoma who had AKT and pAKT expression, whereas it was about 80% in those who did not have AKT or pAKT expression. Taken together, these results indicate that FSH increases the expression of VEGF by upregulating the expression of survivin, which is activated by the PI3K/AKT signaling pathway. Understanding the role of the PI3K/AKT pathway in FSH-stimulated expression of survivin and VEGF will be beneficial for evaluating the prognosis for patients with ovarian serous cystadenocarcinoma and for pursulug effective treatment against this disease.展开更多
Cerebral hypoxia or ischemia results in cell death and cerebral edema, as well as other cellular reactions such as angiogenesis and the reestablishment of functional microvasculature to promote recovery from brain inj...Cerebral hypoxia or ischemia results in cell death and cerebral edema, as well as other cellular reactions such as angiogenesis and the reestablishment of functional microvasculature to promote recovery from brain injury. Vascular endothelial growth factor is expressed in the central nervous system after hypoxic/ischemic brain injury, and is involved in the process of brain repair via the regulation of angiogenesis, neurogenesis, neurite outgrowth, and cerebral edema, which all require vascular endothelial growth factor signaling. In this review, we focus on the role of the vascular endothelial growth factor signaling pathway in the response to hypoxic/ischemic brain injury, and discuss potential therapeutic interventions.展开更多
[目的]运用网络药理学方法探讨小青龙汤治疗慢性肾小球肾炎的潜在作用机制。[方法]借助中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)收集小青龙汤的活性...[目的]运用网络药理学方法探讨小青龙汤治疗慢性肾小球肾炎的潜在作用机制。[方法]借助中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)收集小青龙汤的活性化合物及其作用靶点,借助在线人类孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库和基因组注释数据平台(genome annotation database platform,GeneCard)收集慢性肾小球肾炎的疾病靶点,通过韦恩图2.1确定交集基因;将交集基因导入String 11.0平台,构建蛋白质相互作用(protein protein interaction,PPI)网络;利用DAVID 6.7数据库和Omicshare Tool软件进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。[结果]获得有效化合物149种,药物靶点2447个,疾病靶点2425个;得到潜在靶点154个,通过构建“化合物-靶点”网络图,确定小青龙汤治疗慢性肾小球肾炎的核心成分40个、核心靶点40个。核心成分为槲皮素、山奈酚、β-谷甾醇、柚皮素、木犀草素、黄芩苷、卡维丁、隐品碱等;核心靶点为前列腺素G/H合酶2(prostaglandin G/H synthase 2,PTGS2)、半胱天冬酶-3(caspase-3,CASP3)、雌激素受体1(estrogen receptor 1,ESR1)、一氧化氮合酶2(nitric oxide synthase 2,NOS2)、雄激素受体(androgen receptor,AR)、丝裂原活化蛋白激酶14(mitogen-activated protein kinase 14,MAPK14)等。GO富集分析显示小青龙汤通过血管生成、血管内皮细胞迁移的正调控、脂多糖介导的信号通路、类固醇激素受体活性、细胞外调节蛋白激酶的正调控等生物过程发挥治疗作用,KEGG富集分析显示了血管内皮生长因子(vascular endothelial growth factor,VEGF)信号通路、缺氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)信号通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路、磷脂酰肌醇激酶-蛋白激酶B(phosphatidylinositide 3-kinases-protein kinase B,PI3K-Akt)信号通路和Toll样受体信号通路共5条信号通路。[结论]网络药理学方法研究提示,小青龙汤可能通过调节VEGF信号通路、HIF-1信号通路、TNF信号通路及PI3K/AKT信号通路等发挥抗炎作用,治疗慢性肾小球肾炎。展开更多
文摘There is evidence to suggest that follicle-stimulating hormone （FSH） can facilitate the neovascularization of ovarian cancers by increasing vascular endothelial growth factor （VEGF） expression in cancer cells, although the underlying molecular mechanism of this process is not well known. Therefore, we investigated the effect of FSH on VEGF expression in the ovarian cancer cell lines SKOV-3 and ES-2. Treatment with FSH significantly increased VEGF expression in a dose- and time-dependent manner. In addition, FSH treatment enhanced the expression of survivin and hypoxlainducible factor-1 （HIF-1α）. Knockdown of survivin or HIF-1α suppressed VEGF expression, but only knockdown of survivin inhibited FSH-stimulated VEGF expression. Pretreatment with LY294002, a phosphoinositide 3-kinase （PI3K）/AKT inhibitor, neutralized the enhanced expression of survivin induced by FSH, but treatment with U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, had no such effect. We further showed that ovarian serous cystadenocarcinoma samples had much higher incidence of positive AKT and phosphorylated AKT （pAKT） protein staining than did benign ovarian cystadenoma samples （p 〈 0.01）. The 5-year survival rate was only about 15% in patients with ovarian serous cystadenocarcinoma who had AKT and pAKT expression, whereas it was about 80% in those who did not have AKT or pAKT expression. Taken together, these results indicate that FSH increases the expression of VEGF by upregulating the expression of survivin, which is activated by the PI3K/AKT signaling pathway. Understanding the role of the PI3K/AKT pathway in FSH-stimulated expression of survivin and VEGF will be beneficial for evaluating the prognosis for patients with ovarian serous cystadenocarcinoma and for pursulug effective treatment against this disease.
基金supported by the National Natural Science Foundation of China,No.81401238,81330016,31171020,81172174 and 81270724the grants from Ministry of Education of China,No.313037,20110181130002+2 种基金a grant from State Commission of Science Technology of China,No.2012BAI04B04the grants from Science and Technology Bureau of Sichuan Province of China,No.2012SZ0010,2014FZ0113,2014SZ0149a grant from Clinical Discipline Program(Neonatology)from the Ministry of Health of China,No.1311200003303
文摘Cerebral hypoxia or ischemia results in cell death and cerebral edema, as well as other cellular reactions such as angiogenesis and the reestablishment of functional microvasculature to promote recovery from brain injury. Vascular endothelial growth factor is expressed in the central nervous system after hypoxic/ischemic brain injury, and is involved in the process of brain repair via the regulation of angiogenesis, neurogenesis, neurite outgrowth, and cerebral edema, which all require vascular endothelial growth factor signaling. In this review, we focus on the role of the vascular endothelial growth factor signaling pathway in the response to hypoxic/ischemic brain injury, and discuss potential therapeutic interventions.
