AIM： To investigate the effect of （-）-epigallocatechin-3-gallate （EGCG） on growth of gastric cancer and its possible mechanism. METHODS： Heterotopic tumors were induced by subcutaneously injection of SGC-7901 ce...AIM： To investigate the effect of （-）-epigallocatechin-3-gallate （EGCG） on growth of gastric cancer and its possible mechanism. METHODS： Heterotopic tumors were induced by subcutaneously injection of SGC-7901 cells in nude mice. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density （MVD） by immunohistology. Vascular endothelial growth factor （VEGF） protein level and activation of signal transducer and activator of transcription 3 （Star3） were examined by Western blotting. VEGF mRNA expression was determined by RT-PCR and VEGF release in tumor culture medium by ELISA. VEGF-induced cell proliferation was studied by MTT assay, cell migration by gelatin modified Boyden chamber （Transwell） and in vitro angiogenesis by endothelial tube formation in Matrigel. RESULTS： Intraperitoneal injection of EGCG inhibited the growth of gastric cancer by 60.4%. MVD in tumor tissues treated with EGCG was markedly reduced. EGCG treatment reduced VEGF protein level in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was associated with reduced activation of Star3, but EGCG treatment did not change the total Star3 expression. EGCG also inhibited VEGF-induced endothelial cell proliferation, migration and tube formation. CONCLUSION： EGCG inhibits the growth of gastric cancer by reducing VEGF production and angiogenesis, and is a promising candidate for anti-angiogenic treatment of gastric cancer.展开更多
AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endo...AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.展开更多
Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the c...Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: E-chocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vessel development assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad. VEGF-B group versus 19±4 and 17±6 in Ad. LacZ and PBS group. Conclusion: Direct intramyocardial administration of Ad. VEGF-B can induce focal angiogenesis and result in improvement in regional myocardial function, which may be useful in patients with ischemic heart disease who are not eligible for conventional therapies.展开更多
Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown...Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors(VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells(DCs), macrophages, and lymphocytes further express certain types of VEGF receptors.VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness.This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.展开更多
AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the ...AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg·d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2±12.7 μmol/L Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89±32.07 mm3) compared to the control group (828.21±31.59 mm3) (P<0.05). The MVD of the treated group (19.50±5.32) was markedly decreased compared to the control group (37.40±4.93) (P<0.001). The VEGF expression of the treated group (1.19±0.17) was obviously reduced as compared to the control group (1.90±0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (rs = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.展开更多
Nanoparticles can be involved in biological activities such as apoptosis, angiogenesis, and oxidative stress by themselves. In particular, inorganic nanoparticles such as gold and silica nanoparticles are known to inh...Nanoparticles can be involved in biological activities such as apoptosis, angiogenesis, and oxidative stress by themselves. In particular, inorganic nanoparticles such as gold and silica nanoparticles are known to inhibit vascular endothelial growth factor （VEGF）-mediated pathological angiogenesis. In this study, we show that anti-angiogenic effect of inorganic nanospheres is determined by their sizes. We demonstrate that 20 nm size gold and silica nanospheres suppress VEGF-induced activation of VEGF receptor-2, in vitro angiogenesis, and in vivo pathological angiogenesis more efficiently than their 100 nm size counterparts. Our results suggest that modulation of the size of gold and silica nanospheres determines their inhibitory activity to VEGF-mediated angiogenesis.展开更多
基金Supported by the grants from the National Natural Science Foundation of China, No. 30571833the Natural Science Foundation of Guangdong Province, China, No. 05001785
文摘AIM： To investigate the effect of （-）-epigallocatechin-3-gallate （EGCG） on growth of gastric cancer and its possible mechanism. METHODS： Heterotopic tumors were induced by subcutaneously injection of SGC-7901 cells in nude mice. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density （MVD） by immunohistology. Vascular endothelial growth factor （VEGF） protein level and activation of signal transducer and activator of transcription 3 （Star3） were examined by Western blotting. VEGF mRNA expression was determined by RT-PCR and VEGF release in tumor culture medium by ELISA. VEGF-induced cell proliferation was studied by MTT assay, cell migration by gelatin modified Boyden chamber （Transwell） and in vitro angiogenesis by endothelial tube formation in Matrigel. RESULTS： Intraperitoneal injection of EGCG inhibited the growth of gastric cancer by 60.4%. MVD in tumor tissues treated with EGCG was markedly reduced. EGCG treatment reduced VEGF protein level in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was associated with reduced activation of Star3, but EGCG treatment did not change the total Star3 expression. EGCG also inhibited VEGF-induced endothelial cell proliferation, migration and tube formation. CONCLUSION： EGCG inhibits the growth of gastric cancer by reducing VEGF production and angiogenesis, and is a promising candidate for anti-angiogenic treatment of gastric cancer.
基金Supported by Grants from the Japan Society for the Promotion of Science,Grant-in-Aid for Scientific Research(B),No.22300264
文摘AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.
基金Supported by the National Natural Science Foundation of China (No. 39970735)
文摘Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: E-chocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vessel development assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad. VEGF-B group versus 19±4 and 17±6 in Ad. LacZ and PBS group. Conclusion: Direct intramyocardial administration of Ad. VEGF-B can induce focal angiogenesis and result in improvement in regional myocardial function, which may be useful in patients with ischemic heart disease who are not eligible for conventional therapies.
基金supported by grants from the key program of the National Basic Research Program of China (973 program) (Grant No. 2012CB9333004)the National Natural Science Foundation of China (Grant No. 81401888)
文摘Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors(VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells(DCs), macrophages, and lymphocytes further express certain types of VEGF receptors.VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness.This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.
基金Supported by National Natural Science Foundation of China, No. 30271516
文摘AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg·d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2±12.7 μmol/L Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89±32.07 mm3) compared to the control group (828.21±31.59 mm3) (P<0.05). The MVD of the treated group (19.50±5.32) was markedly decreased compared to the control group (37.40±4.93) (P<0.001). The VEGF expression of the treated group (1.19±0.17) was obviously reduced as compared to the control group (1.90±0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (rs = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.
文摘Nanoparticles can be involved in biological activities such as apoptosis, angiogenesis, and oxidative stress by themselves. In particular, inorganic nanoparticles such as gold and silica nanoparticles are known to inhibit vascular endothelial growth factor （VEGF）-mediated pathological angiogenesis. In this study, we show that anti-angiogenic effect of inorganic nanospheres is determined by their sizes. We demonstrate that 20 nm size gold and silica nanospheres suppress VEGF-induced activation of VEGF receptor-2, in vitro angiogenesis, and in vivo pathological angiogenesis more efficiently than their 100 nm size counterparts. Our results suggest that modulation of the size of gold and silica nanospheres determines their inhibitory activity to VEGF-mediated angiogenesis.
