Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.
Humans ; Female ; Medicine, Chinese Traditional ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Angiogenesis ; Angiogenesis Inhibitors/therapeutic use* ; Ovarian Neoplasms/genetics* ; Neovascularization, Pathologic/genetics*

Vascular endothelial growth factor is a potent inducer of angiogenesis identified in recent years, and its relationship with ischemic cerebral vascular diseases is a hotspot for many investigators at present. In this review, we focus on the recent evidence for VEGF expression, biological effect and its role in the treatment and prognostication of ischemic cerebral vascular disease.
Angiogenesis Inducing Agents ; therapeutic use ; Brain Ischemia ; drug therapy ; metabolism ; Cerebral Infarction ; drug therapy ; metabolism ; Humans ; Neovascularization, Physiologic ; drug effects ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics ; therapeutic use

OBJECTIVETo investigate the effect of G4PAMAM/VEGFASODN compound on expression of VEGF and VEGF mRNA in MDA-MB-231 breast cancer cells and the growth inhibition of vascular endothelial cells.

METHODSThe diameter of G4PAMAM/VEGFASODN granule was measured by transmission electron microscopy, and its stability under different pH was also observed. The efficiency of transfection in vitro was detected by flow cytometer and the positively transfected cells were detected by laser scanning confocal microscope. The survival rate and the inhibitory rate of vascular endothelial cells were determined by MTT assay. The expression of protein VEGF was detected by immunohistochemical method and the expression of VEGF mRNA was detected by RT-PCR.

RESULTThe diameter of G4PAMAM/VEGFASODN granules was about 10 nm and it arranged as homogeneous netlike. Under pH 5-10 G4PAMAM/VEGFASODN presented highly stable and no dissociation was observed with different charge ratios. The 48-hour transfection rate of G4PAMAM/VEGFASODN in charge ratio of 1:40 was significantly higher than that of the lipofectamine group. None of the transfection products in each group showed cell toxicity. The staining of VEGF protein in the cytoplasm of MDA-MB-231 cells after G4PAMAM/ASODN transfection weakened markedly, and the positive expression rate decreased. Meanwhile, the VEGF mRNA expression was also decreased.

CONCLUSIONWith good stability and transfection rate, compound G4PAMAM/VEGFASODN can be a promising new nanometer vector of gene transfer system. The G4PAMAM/VEGFASODN can inhibit the expression of VEGF gene specifically and efficiently, which may be used for in vivo animal experiment.

Angiogenesis Inhibitors ; genetics ; pharmacology ; Breast Neoplasms ; blood supply ; genetics ; pathology ; Cell Line, Tumor ; Dendrimers ; pharmacology ; Humans ; Nanoparticles ; Nylons ; pharmacology ; Oligonucleotides, Antisense ; pharmacology ; RNA, Messenger ; metabolism ; Transfection ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Carbolines ; chemistry ; pharmacology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Epidermal Growth Factor ; genetics ; metabolism ; Fibroblast Growth Factors ; genetics ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Neovascularization, Physiologic ; drug effects ; Picrasma ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; Receptor, TIE-2 ; genetics ; metabolism ; Zebrafish ; embryology

AIM: The compound B19 (C21H22O5) is a newly synthesized, mono-carbonyl analog of curcumin that has exhibited potential antitumor effects. This present study was performed to identify the anti-angiogenic activity of this compound. METHODS AND RESULTS: B19 inhibited migration and tube formation of human umbilical vein endothelial cells, and arrested microvessel outgrowth from rat aortic rings. In addition, B19 suppressed the neovascularization of chicken chorioallantoic membrane. Mechanistic studies revealed that B19 suppressed the downstream protein kinase activation of vascular endothelial growth factor (VEGF) by decreasing phosphorylated forms of serine/threonine kinase Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, with or without stimulating vascular endothelial growth factor (VEGF). CONCLUSIONS B19 exerted anti-angiogenic activity in vitro and ex vivo, which suggests that it merits further investigation as a promising anticancer angiogenesis compound.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Aorta ; drug effects ; metabolism ; Cell Movement ; drug effects ; Curcumin ; analogs & derivatives ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; In Vitro Techniques ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

Shouwu is a traditional Chinese medicine (TCM) with neuroprotective effect. Shouwu Yizhi decoction (SYD) was designed based on TCM theory. However, little is known about the roles of SYD in Vascular dementia (VaD). The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion (I/R) rat model to induce VaD. SYD administration (54 mg·kg) for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion (MCAO) rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test. Moreover, SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats, thereby alleviating VaD. Mechanistically, SYD caused increases in the expression of vascular endothelial growth factor (VEGF), CD34 and CD31, compared with the MCAO rats in coronal hippocampus. Simultaneously, the expression level of miR-210 was elevated significantly after SYD administration, compared with the vehicle rats (P < 0.01). The expression of Notch 4 at both mRNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats (P < 0.05). Overall, the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced miR210 expression to activate Notch pathway, and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats, ultimately enhancing the cognition and memory of MCAO rats. Therefore, our findings preliminarily identified the effect and the mechanism of action for SYD on VaD in rats. SYD could be a potential candidate in treatment of VaD.
Angiogenesis Inducing Agents ; administration & dosage ; Animals ; Dementia, Vascular ; drug therapy ; genetics ; metabolism ; psychology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Memory ; drug effects ; Neuroprotective Agents ; administration & dosage ; Rats ; Rats, Wistar ; Receptor, Notch4 ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

BACKGROUND/AIMS: This study aimed to better understand gene expression profiles of human hepatic stellate cell (HSC) activation and the relationship with the Wnt signaling pathway. METHODS: The global transcript levels in platelet derived growth factor-BB (PDGF-BB)-stimulated hTERT HSCs were analyzed using oligonucleotide microarrays. Oligonucleotide microarrays with 19K human oligo chips were performed to obtain gene expression profiles associated with proliferation in human hTERT HSCs. The microarray data was verified by real time quantitative PCR and expression of the components of Wnt signaling was analyzed by Western blot. RESULTS: Microarray data showed 243 up-regulated and 265 down-regulated genes in PDGF-BB-treated HSCs. The changes in expression of glypican3 and BH3 interacting domain death agonist (BID) mRNA in real time quantitative PCR, especially among the highly up- or down-regulated genes, were statistically consistent with the microarray data. The Wnt signaling pathway components, frizzled10 (FZD10) and calcium/calmodulin-dependent protein kinase II alpha (CAMK2A), showed increased expression in the short time course microarray and the up-regulation of FZD10 also occurred at the protein level. Our data showed various gene expression profiles during activation of human HSC. CONCLUSIONS: The up-regulated expression of FZD10 and CAMK2A suggests that the Wnt/Ca2+ signaling pathway is active in hTERT HSCs and may participate in HSC activation and proliferation
Angiogenesis Inducing Agents/*pharmacology ; Blotting, Western ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/metabolism ; Cell Line ; Cell Proliferation ; Frizzled Receptors/genetics/metabolism ; Gene Expression Profiling ; Hepatic Stellate Cells/cytology/*metabolism ; Humans ; Oligonucleotide Array Sequence Analysis ; Platelet-Derived Growth Factor/*pharmacology ; Polymerase Chain Reaction ; Receptors, G-Protein-Coupled/genetics/metabolism ; *Signal Transduction ; Up-Regulation ; Wnt Proteins/genetics/*metabolism

OBJECTIVETo study the effects of the generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide (G4PAMAM/VEGFASODN) compound on the expressions of vascular endothelial growth factor (VEGF) and its mRNA of breast cancer cells and on the inhibition of vascular endothelial cells.

METHODSWe examined the morphology of G4PAMAM/VEGFASODN compound and its pH stability, in vitro transfection efficiency and toxicity, and the expressions of VEGF and its mRNA. Methyl thiazolyl tetrazolium assay was used to detect the inhibitory function of the compound on vascular endothelial cells.

RESULTSThe compound was about 10 nm in diameter and was homogeneously netlike. From pH 5 to 10, it showed quite a buffered ability. The 48-h transfection rate in the charge ratio of 1:40 was 98.76%, significantly higher than that of the liposome group (P<0.05). None of the transfection products showed obvious toxicity on the cells. The expressions of both VEGF protein and its mRNA after G4PAMAM/VEGFASODN transfection decreased markedly.

CONCLUSIONWith a low toxicity, high safety, and high transfection rate, G4PAMAM/VEGFASODN could be a promising gene vector. Specifically, it inhibits VEGF gene expression efficiently, laying a basis for further in vivo animal studies.

Angiogenesis Inhibitors ; genetics ; Breast Neoplasms ; blood supply ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dendrimers ; Gene Expression Regulation ; drug effects ; Humans ; Hydrogen-Ion Concentration ; Microscopy, Electron, Transmission ; Nylons ; Oligodeoxyribonucleotides, Antisense ; genetics ; pharmacology ; ultrastructure ; RNA, Messenger ; genetics ; Transgenes ; genetics ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; ultrastructure

Until recently, vascular endothelial growth factor (VEGF) was the only growth factor proven to be specific and critical for blood vessel formation. Other long-known factors, such as the fibroblast growth factors (FGFs), platelet-derived growth factor, or transforming growth factor-beta, had profound effects in endothelial cells. But such factors were nonspecific, in that they could act on many other cells, and it seemed unlikely that these growth factors would be effective targets for treatment of endothelial cell diseases. A recently discovered endothelial cell specific growth factor, angiopoietin, has greatly contributed to our understanding of the development, physiology, and pathology of endothelial cells (Davis et al., 1996; Yancopoulos et al., 2000). The recent studies that identified and characterized the physiological and pathological roles of angiopoietin have allowed us to widen and deepen our knowledge about blood vessel formation and vascular endothelial function. Therefore, in this review, we describe the biomedical significance of these endothelial cell growth factors, the angiopoietins, in the vascular system under normal and pathological states.
Alternative Splicing ; Angiogenesis Factor/genetics/*metabolism ; Animal ; Cell Survival ; Endothelial Growth Factors/metabolism ; Endothelium, Vascular/cytology/*physiology ; Hematopoiesis/physiology ; Human ; Intercellular Signaling Peptides and Proteins/metabolism ; Lymphokines/metabolism ; Membrane Glycoproteins/genetics/*metabolism ; Neoplasm Proteins/metabolism ; Neovascularization, Pathologic ; Neovascularization, Physiologic ; Signal Transduction/physiology ; Urogenital System/physiology

Our previous studies have demonstrated the effects of brain derived neurotrophic factor (BDNF) on promoting proliferation of multiple myeloma (MM) cells and inducing angiogenesis in MM in vitro. To further investigate whether the PI3K/Akt and MEK1/ERK pathway play a role in the BDNF-induced angiogenesis in vitro and to explore the further molecular mechanisms, two ways to establish human myeloma xenograft animal model were developed, their advantages and disadvantages were elucidated. The phosphorylation of AKT and ERK1/2 were detected in human umbilical vein endothelial cells (HUVECs) by Western blot. The angiogenic activity in vitro was evaluated by transwell migration assay and tubule formation assay. Cell proliferation was determined by crystal violet staining. Cell apoptosis was detected by FITC-Annexin-V/PI double staining and flow cytometry. The results showed that the BDNF activated the PI3K/Akt and MEK1/ERK pathway in the time-dependent manner. Ly294002 and PD98059 blocked the activation of Akt and ERK1/2 respond to BDNF. 100 ng/ml BDNF significantly increased HUVEC tube formation, migration and proliferation in vitro at a similar degree of 25 ng/ml VEGF. Furthermore, tube formation of HUVECs toward BDNF was significantly inhibited by 57% and 40% with 20 micromol/L Ly294002 and 20 micromol/L PD98059 treatment, respectively. At the same time, Ly294002 and PD98059 reduced the BDNF-induced migration of HUVECs by 74% and 36%, respectively. While BDNF-induced survival was only blocked by Ly294002 and BDNF-induced proliferation was only inhibited by PD98059. It is concluded that BDNF promotes angiogenesis of HUVECs in vitro. ERK and Akt are two crucial events in BDNF-mediated signal transduction leading to HUVECs angiogenesis by different mechanisms. Moreover, the latter is more important.
Angiogenesis Inducing Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; pharmacology ; Chromones ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Flavonoids ; pharmacology ; Humans ; MAP Kinase Kinase 2 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; Morpholines ; pharmacology ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Signal Transduction ; Umbilical Veins ; cytology