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1.
Toxicology ; 274(1-3): 27-33, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20452389

RESUMO

Hypoxia is a common characteristic feature of solid tumors, and carcinoma cells are known to secrete many growth factors. These growth factors, such as vascular endothelial growth factor (VEGF), play a major role in the regulation of tumor angiogenesis and metastasis. In this study, the effect of gamma-tocotrienol, a natural product commonly found in palm oil and rice bran, on the accumulation of HIF-1alpha protein and the paracrine secretion of VEGF in human gastric adenocarcinoma SGC-7901 cell line induced by cobalt(II) chloride (as a hypoxia mimic) was investigated. These results showed that cobalt(II) chloride induced the high expression of VEGF in SGC-7901 cells at dose of 150 micromol/L for 24h. Both basal level and cobalt(II) chloride-induced HIF-1alpha protein accumulation and VEGF paracrine secretion were inhibited in SGC-7901 cells treated with gamma-tocotrienol at 60 micromol/L treatment for 24 h. U0126, a MEK1/2 inhibitor, decreased the expression of HIF-1alpha protein and the paracrine secretion of VEGF under normoxic and hypoxic conditions. In this study, gamma-tocotrienol also significantly inhibited the hypoxia-stimulated expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). The mechanism seems to involve in inhibiting hypoxia-mediated activation of p-ERK1/2, it leads to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF secretion. These data suggest that HIF-1alpha/VEGF could be a promising target for gamma-tocotrienol in an effective method of chemoprevention and chemotherapy in human gastric cancer.


Assuntos
Proteínas/metabolismo , Neoplasias Gástricas/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adenocarcinoma , Linhagem Celular , Cromanos , Cobalto/farmacologia , Guanilato Ciclase , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/farmacologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/farmacologia , Neovascularização Patológica , Fosforilação , Proteínas/farmacologia , Receptores Citoplasmáticos e Nucleares , Transdução de Sinais/efeitos dos fármacos , Guanilil Ciclase Solúvel , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/patologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/farmacologia , Vitamina E/análogos & derivados
2.
Zhongguo Zhong Yao Za Zhi ; 30(9): 694-6, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-16075737

RESUMO

OBJECTIVE: To observe the regulative effect of opuntia powder on blood lipids in wistar rats and to explore its mechanism. METHOD: Forty normal rats were divided into four groups:control group (fed with basal feed), opuntia high, middle and low dosage groups (fed with basal feed and opuntia powder of high, middle and low dosage. The influence of opuntia powder on serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), arteriosclerosis index (AI), serum malondialdehyde (MDA), superoxide dismutase (SOD) were observed. (2) All of the hyperlipemia wistar rats for experiments were divided into four groups: model control group and other three groups (high, middle, low dosage groups respectively). Three weeks later, samples of blood were taken for survey of levels of TC, TG HDL-C, LDL-C, AI, MDA, SOD. RESULT: After opuntia powder treatment,the level of TC in nomal wistar rats was decreased. However, there was no significant difference comparing with control group (P > 0.05). The serum MAD level in the low, middle and high dosage groups were all obviously decreased, which were significantly lower than that in the control group. The SOD activities were all higher than that in the control group. The level of TC, LDL-C, AI (P < 0.01), TG (P < 0.05) were lower significantly in hyperlipemia wistar rats after treated by opuntia powder of high, middle and low dosage. The down-regulation of blood lipids was related with the dosage of opuntia powder. CONCLUSION: The opuntia powder may regulate the level of blood lipids in normal and hyperlipemia wistar rats. The effect is more obviously in hyperlipemia rats than that in normal rats.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/sangue , Lipídeos/sangue , Opuntia , Plantas Medicinais , Animais , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Masculino , Malondialdeído/sangue , Camundongos , Opuntia/química , Plantas Medicinais/química , Pós , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Triglicerídeos/sangue
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