The instability of atherosclerotic plaque would lead to the rupture of plaque, even acute coronary syndrome (ACS). To prevent the internal atherosclerosis plaque angiogenesis may play a very important role in stabilizing the vulnerable plaque. Traditional Chinese drugs show potential advantages in stabilizing AS plaque by its characteristics of multi-way, multi-link and multi-target all-sided treatment.
Animals ; Arteriosclerosis ; classification ; pathology ; Coronary Artery Disease ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; Neovascularization, Pathologic ; prevention & control ; Phytotherapy

Malignant tumor is the common disease that threaten severely to people's health. Formulae of traditional Chinese medicine (FTCM), as the major component of traditional drugs, has played more important role on the prevention and cure to tumor. The Folkman's theory that tumorous growth depends on tumor neovascularization has been confirmed so many years, so to inhibit the tumor angiogenesis, is an important path to treat tumor. The research of FTCM to antagonizing tumor angiogenesis in our country has been started more lately. Since it has been reported some FTCMs can inhibit angiogenesis, and it also exists many problems. The article summarized the correlated research of FTCM to antagonize tumor angiogenesis for the past several years, and according this, analyzed, stated and commented to the problems, countermeasures, development and direction of PTCM to antagonize tumor angiogenesis.
Animals ; Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Neoplasms ; drug therapy ; pathology ; prevention & control ; Neovascularization, Pathologic ; drug therapy ; prevention & control

OBJECTIVETo investigate the effects of Shexiang Baoxin Pill (SBP) in intervening atherosclerosis and myocardial infarction (AS-MI) in experimental animals, and inspect its influences on angiogenesis.

METHODSTwenty male New-Zealand rabbits were made into AS-MI model, and randomly divided into 2 groups equally. Group A was fed with high-fat diet for control; Group B was fed with high-fat diet but intervened with SBP. The cardiac function and the positive area of plaque were determined. The CD34 positive response intensity at infarcted marginal zone and aorta vessel wall, and the capillary density of myocardium were measured by immunohistochemical staining. In addition, the protein expressions of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by Western blot.

RESULTSCompared to Group A, the cardiac function was obviously improved (P<0.05) and the plaque positive area (%) was significantly decreased in Group B (45.82 +/- 3.68 vs 82.56 +/- 4.97, P<0.01). The CD34 positive response intensity and the capillary density as well as VEGF and VEGFR-2 expressions in infarcted marginal zone in Group A were higher than those in Group B (P<0.01); but these parameters at aorta vessel walls were lower in Group A than in Group B (P<0.01).

CONCLUSIONSBP could advance the angiogenesis in the marginal zone of infarction, improve heart function, and embarrass angiogenesis in atherosclerotic plaque.

Animals ; Atherosclerosis ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Myocardial Ischemia ; physiopathology ; Neovascularization, Pathologic ; physiopathology ; prevention & control ; Neovascularization, Physiologic ; drug effects ; Plaque, Atherosclerotic ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

BACKGROUNDGinsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.

METHODSThe experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.

RESULTSIn the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.

CONCLUSIONSGinsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

Animals ; Cell Line, Tumor ; Female ; Ginsenosides ; pharmacology ; Humans ; Lung Neoplasms ; prevention & control ; secondary ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; prevention & control ; Ovarian Neoplasms ; drug therapy ; pathology

OBJECTIVETo study the acting mechanism of Cordyceps mycelia extract (CME) for antagonizing hepatic sinusoidal capillarization (HSC) in rats with dimethylnitrosamine (DMN) induced liver cirrhosis.

METHODSRat liver cirrhosis model was established by peritoneal injection of DMN 10 mg/kg 3 times a week for 4 weeks. To rats in the CME-prevented group CME were administrated at a dose of 10 mL/kg, once a day, for 4 weeks. The observation time points were scheduled on the 3rd day (d3), and at the end of the 2nd (W2) and 4th week (W4) after modeling, and the following items were observed: hepatic ultrastructure was observed under electron microscope; expressions of CD44, von Willebrand factor (vWF) and type IV collagen (Col lV) in the liver sinusoidal walls by immunohistochemistry; matrix metalloproteinase-2 and-9 (MMP-2, MMP-9) activity under zymogram method; and serum hyaluronic acid (HA) content by radioimmunoassay.

RESULTSObservation at d3 showed MMP-2 and MMP-9 activity significantly increased, Col IV deposition and CD44 positive staining decreased, vWF positive staining increased in the liver sinusoidal walls, the fenestrae in the sinusoidal endothelial cells (SECs) decreased, and serum HA content increased (P<0.05); at W4, SECs defenestration and sub-SECs basal membrane formation were shown. In the CME-prevented group MMP-2 and MMP-9 activity significantly decreased (P<0.05); defenestration and basal membrane formation alleviated in the early stage (d3, W4); and at W2 and W4 decreases of HA content and vWF positive staining were shown, with increase of CD44 positive staining (P<0.05), more SECs fenestrae, and alleviated basal membrane formation.

CONCLUSIONSThe elevation of MMP-2 and MMP-9 activity in the early stage, which degrades the Col IV normally distributed under the sinusoidal endothelium, is an important factor for HSC formation. CME could inhibit the initiation of HSC by decreasing MMP-2 and MMP-9 activity in the early stage, and prevent its formation by decreasing SECs injury and phenotypic changes.

Animals ; Capillaries ; pathology ; Cordyceps ; Dimethylnitrosamine ; adverse effects ; Hepatic Veins ; cytology ; drug effects ; pathology ; Liver ; blood supply ; Liver Cirrhosis, Experimental ; pathology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mycelium ; Neovascularization, Pathologic ; prevention & control ; Rats ; Rats, Wistar

The contribution of angiogenesis inhibitor TNP-470 to the growth and metastasis of ACHN renal cell carcinoma (RCC) was studied. TNP-470 (40 mg/kg, every two days) was administrated to BABL/c nude mice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31 days and the weight and volume of subcutaneous tumors as well as foci of lung metastasis were measured. The microvascular density (MVD) of the tumor as well as the PCNA index and apoptotic index of the tumor cells were evaluated immunohistochemically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was observed in TNP-470-treated mice. Compared with the control group, the MVD was decreased markedly (P < 0.01) and the apoptotic index was increased significantly (P < 0.01) in the treated group. The tumor volume was positively correlated to the MVD (r = 0.7144, P < 0.01) and inversely correlated to the apoptotic index (r = -0.8607, P < 0.01), and MVD was conversely correlated to the apoptotic index. It was determined that TNP-470 could effectively inhibit angiogenesis of ACHN RCC, which resulting in ischemia and hypoxia, leading to increased apoptosis, thus obviously suppressing the growth and metastasis of ACHN RCC in nude mice.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; drug effects ; Carcinoma, Renal Cell ; drug therapy ; pathology ; secondary ; Cell Division ; Cyclohexanes ; Female ; Kidney Neoplasms ; drug therapy ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; prevention & control ; Random Allocation ; Sesquiterpenes ; pharmacology

OBJECTIVETo investigate the therapeutic effect of thyroid hormone in nude mice bearing human pancreatic cancer xenograft.

METHODSA BALB/c nude mouse model bearing pancreatic cancer was established with human pancreatic cancer cell line Bx-PC3. The mouse models were divided randomly into 5 groups, namely the control group treated with distilled water, high and low concentrations of thyroid hormone (T3) groups, and high and low concentration of propylthiouracil (PTU) groups. After intervention for 21 days, the changes in body weight and xenograft tumor volume and weight were measured, and the serum T3 concentration was detected by ELISA assay. The expression of proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were detected using immunohistochemistry.

RESULTSThe body weight of nude mice in T3 groups was significantly reduced after intervention, while that in PTU groups showed no obvious changes. Compared with PTU groups and control group, T3 groups showed significantly reduced tumor volume and weight (P<0.05) with also reduced PCNA expression and MVD, but these effect did not exhibit a dose dependence (P>0.05).

CONCLUSIONThyroid hormone can inhibit the growth of human pancreatic cancer in nude mice by suppressing the proliferation and angiogenesis of the tumor cells, suggesting the potential value of thyroid hormone in pancreatic cancer therapy.

Animals ; Cell Line, Tumor ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Neovascularization, Pathologic ; prevention & control ; Pancreatic Neoplasms ; blood supply ; pathology ; Proliferating Cell Nuclear Antigen ; metabolism ; Triiodothyronine ; pharmacology ; Xenograft Model Antitumor Assays

OBJECTIVEThe purpose of this study was to investigate the effect of an angiogenesis inhibitor (TNP-470) on the ultra micro-structural morphological changes of GNM cell line, which was derived from human oral squamous cell carcinomas in vitro.

METHODSThe GNM cells were cultured and, the effect of TNP-470 on ultra micro-structural morphological changes of GNM cells was observed under the inverted microscope, the scanning electron microscope (SEM) and the transmission electron microscope (TEM).

RESULTSNumerous round cells, shrinkage of cellular membrane and dead cells were observed 48 hours after 2 micrograms/ml of TNP-470 was added into the GNM cellular suspension. After 72 hours, GNM cells became shortened and, the number of microvilli of the cellular surface was observed under the SEM and TEM. A large number of GNM cells turned into necrosis, accompanying with the destruction of mitochondria and endoplasmic reticula.

CONCLUSIONTNP-470 has a strong tumor cytotoxic effect on GNM cells, which may be due to its destructibility on mitochondria and endoplasmic reticula of GNM cells. TNP-470 can alter the surface structure of GNM cell membrane, which suggests that TNP-470 may interrupt the metastasis of GNM cells.

Angiogenesis Inhibitors ; pharmacology ; Antibiotics, Antineoplastic ; pharmacology ; Carcinoma, Squamous Cell ; blood supply ; pathology ; Cyclohexanes ; Gingival Neoplasms ; blood supply ; pathology ; Humans ; Lymphatic Metastasis ; Neovascularization, Pathologic ; prevention & control ; Sesquiterpenes ; pharmacology ; Tumor Cells, Cultured

BACKGROUNDRNA interference (RNAi) technology is emerging as a very potent tool to generate a cellular knockdown of a desired gene. The aim of this study was to explore whether RNAi targeting vascular endothelial growth factor-C (VEGF-C) could inhibit colorectal tumor lymphangiogenesis and tumor growth.

METHODSWe used vector-based RNAi to inhibit VEGF-C expression in colon cancer in vitro and in vivo. VEGF-C expression was quantified by real-time polymerase chain reaction and Westen blotting. To establish LoVo cell tumor xenografts in mice, we subcutaneously inoculated 1.0 x 10(6) LoVo cells in nude mice; after injection, tumors were allowed to grow for 4 weeks until the volume reached (75.8+/-55.8) mm(3). The mice were then randomly divided into two groups: (1) the VEGF-C-siRNA group (n=10) received direct injection of "therapeutic" plasmid 50 microg of LoVo-VEGF-C-siRNA into the tumor mass; (2) the control group (n=10) were injected with LoVo-control in 20 microl of sterile 0.9% NaCl solution into the tumor mass. Tumor growth, microlymphatics and microvessels were compared for mice administered either systemic VEGF-C-siRNA or control over 4 weeks.

RESULTSThe mRNA and protein expression of VEGF-C in the colon tumor cell line, LoVo, stably transfected with a VEGF-C-siRNA vector, were significantly downregulated 45.3% and 35.3% respectively. In vivo, four weeks after injection, the tumor volume were significantly smaller in VEGF-C-siRNA group than in LoVo-control group ((314.8+/-54.8) mm(3) vs (553.9+/-90.1) mm(3)); the incidences of lymph node metastasis (30%) in VEGF-C-siRNA were significantly inhibited compared with LoVo-control group (70%); in VEGF-C-siRNA group, the number of microlymphatics per microscopic field was (5.3+/-0.7) and the number of microvessels per microscopic field was (24.2+/-6.5) decreased compared with LoVo-control group (12.5+/-6.9) and (42.1+/-7.4) (all P<0.001).

CONCLUSIONInhibition of VEGF-C expression using siRNA-mediated gene silencing vectors reduced lymphangiogenesis and lymph node metastasis and enhanced survival.

Animals ; Cell Line, Tumor ; Colorectal Neoplasms ; blood supply ; pathology ; therapy ; Genetic Vectors ; Humans ; Lymphangiogenesis ; Lymphatic Metastasis ; Mice ; Neovascularization, Pathologic ; prevention & control ; RNA Interference ; RNA, Small Interfering ; genetics ; Vascular Endothelial Growth Factor C ; antagonists & inhibitors ; genetics

In order to explore the probability of curcumin treating multiple myeloma (MM) via the inhibition of angiogenesis, the expressions of brain derived neurotrophic factor (BDNF) and its specific receptor in human MM cells and endothelial cells were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The angiogenic activity was evaluated by endothelial cell migration assay and tubule formation assay in vitro. The results showed that exogenous BDNF significantly induced endothelial cell tubule formation and endothelial cell migration, these two effects were inhibited by curcumin. Furthermore, BDNF was detected in the MM cell and TrkB was detected in the endothelial cell and curcumin depressed the mRNA expression of BDNF and TrkB in the dose- and time-dependent manners. It is concluded that BDNF is a novel angiogenesis protein. Curcumin interrupts the interaction between multiple myeloma cells and endothelial cells by reducing TrkB expression in endothelial cells and inhibiting BDNF production in multiple myeloma cells, eventually, resulting in inhibition of angiogenesis. This is probably one part of the mechanism of the curcumin treating MM via the inhibition of angiogenesis.
Angiogenesis Inhibitors ; pharmacology ; Antineoplastic Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; antagonists & inhibitors ; biosynthesis ; genetics ; Cell Line, Tumor ; Curcumin ; pharmacology ; Endothelial Cells ; cytology ; Humans ; Multiple Myeloma ; blood supply ; pathology ; Neovascularization, Pathologic ; prevention & control ; RNA, Messenger ; biosynthesis ; genetics