Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods...Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.展开更多
AIM: To determine the inhibitory effect of the adenovirus- based angiopoietin-1 (Ang-1) targeted small interfering RNA expression system (Ad/Ang-1si) on the expression of the Ang-1 gene, cell growth and apoptosis in h...AIM: To determine the inhibitory effect of the adenovirus- based angiopoietin-1 (Ang-1) targeted small interfering RNA expression system (Ad/Ang-1si) on the expression of the Ang-1 gene, cell growth and apoptosis in human esophageal cancer cell line Eca109. METHODS: siRNA-expressing adenovirus targeting Ang-1 gene was constructed using the Ad Easy System. Cultured Eca109 cells were transfected with Ad/Ang-1si (Eca109/Ang-1si), and Ad/si was used to infect Eca109 cells as control (Eca109/si). Ang-1 gene expression and concentration was determined with RT-PCR and ELISA, respectively. Human umbilical vein endothelial cell (HUVEC) migration and proliferation were analyzed. After s.c. injection into athymic nu/nu mice, the tumor growth, vessel density and apoptosis of each group was also determined. RESULTS: HUVEC migration induced by conditioned medium from Ang-1si-transfected Eca109 cells was significantly less than that induced by conditioned medium from Eca109 cells and control adenovirus- transfected Eca109 cells. Furthermore, after s.c. injection into athymic nu/nu mice, the tumor growth and cell apoptosis of Ad/Ang-1si -expressing Eca109 cells was significantly lower than that of parental or control adenovirus-transfected cells. Vessel density assessed by CD31 immunohistochemical analysis and Ang-1 expression by RT-PCR were also decreased. CONCLUSION: The targeting Ang-1 may provide a therapeutic option for esophageal cancer.展开更多
Objective: To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods: Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was admini...Objective: To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods: Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was administrated intraperitoneally to investigate the impact of SU5416 on tumor angiogenesis and growth in vivo. 32 mice were treated with SU5416 at two different doses every day until the end-point. As a control, 8 mice received no treatment and 8 mice were treated with vehicle (DMSO) only after implantation. Results: Median survival in the treated group was statistically longer compared to that in the control groups (P < 0.05) and no significant systemic adverse was observed. Histological analysis of the treated tumors showed an increase in necroses and reduced in angiogenesis compared to the control tumors. Furthermore, the percent of apoptotic cells increased in the treated tumors by FCM, the expressions of VEGF and KDR had no change after SU5416 administration by western blot. Conclusion: SU5416 may be useful therapeutics drug that specifically inhibits the enzymatic activity of KDR kinase and could down regulate the tumor angiogenesis.展开更多
Objective To compare the different effects of endothelia progenitor cells （ EPCs ） or basic fibroblast growth factor （b-FGF） intromyocardial infusion on cardiac function and neovascularization for dilated cardiomy...Objective To compare the different effects of endothelia progenitor cells （ EPCs ） or basic fibroblast growth factor （b-FGF） intromyocardial infusion on cardiac function and neovascularization for dilated cardiomyopathy（ DCM） rats. Methods Fifty adult female rats received inguinal subcutaneous injections of isoproterenol （ISO, 250 mg/kg） for induction of DCM. Four weeks later, the model rats were randomly divided into EPCs group, b-FGF group and control group. The 2×106 EPCs （ resolved in 100 μL PBS） , 100 μL b-FGF （ lO0 μg/mL ） and 100 μL PBS were evenly transplanted into the myocardium of EPCs group, b-FGF group and control group, respectively. Three months later, echocardiographic examination and regional myocardial blood flow （RMBF） measurement were performed. EPCs were traced by fluorescence in situ hybridization （FISH）. The protein and mRNA expression of b-FGF in each group was measured by ELISA assay and reverse transcription-polymerase chain reaction （ RT-PCR ） . Results Three months after transplantation, sry positive cells were detected only in EPCs group. The cardiac function as well as RMBF was significantly improved in EPCs group compared with b-FGF group or control group. There was higher capillary density in EPCs group. The protein and mRNA expression of b-FGF was stronger than b-FGF group and control group. Conclusion Transplantation of EPCs can improve cardiac function, induce neovascularization and increase RMBF for DCM rats. The treatment with EPCs has better effect than administration of b-FGF alone.展开更多
Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.T...Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.The transcription factor HIF-1 mediates cellular response to hypoxia by promoting processes,such as glycolysis and angiogenesis.Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance.Therefore,HIF-1 is a viable target for cancer therapy.This review summarizes agents that have been described in the literature as HIF-1 inhibitors.The majority of these compounds are indirect inhibitors of HIF-1.展开更多
文摘Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.
基金The Natural Science Foundation of China, No.30471718
文摘AIM: To determine the inhibitory effect of the adenovirus- based angiopoietin-1 (Ang-1) targeted small interfering RNA expression system (Ad/Ang-1si) on the expression of the Ang-1 gene, cell growth and apoptosis in human esophageal cancer cell line Eca109. METHODS: siRNA-expressing adenovirus targeting Ang-1 gene was constructed using the Ad Easy System. Cultured Eca109 cells were transfected with Ad/Ang-1si (Eca109/Ang-1si), and Ad/si was used to infect Eca109 cells as control (Eca109/si). Ang-1 gene expression and concentration was determined with RT-PCR and ELISA, respectively. Human umbilical vein endothelial cell (HUVEC) migration and proliferation were analyzed. After s.c. injection into athymic nu/nu mice, the tumor growth, vessel density and apoptosis of each group was also determined. RESULTS: HUVEC migration induced by conditioned medium from Ang-1si-transfected Eca109 cells was significantly less than that induced by conditioned medium from Eca109 cells and control adenovirus- transfected Eca109 cells. Furthermore, after s.c. injection into athymic nu/nu mice, the tumor growth and cell apoptosis of Ad/Ang-1si -expressing Eca109 cells was significantly lower than that of parental or control adenovirus-transfected cells. Vessel density assessed by CD31 immunohistochemical analysis and Ang-1 expression by RT-PCR were also decreased. CONCLUSION: The targeting Ang-1 may provide a therapeutic option for esophageal cancer.
基金a grant from the National Key Project of Scientific and Technical Supporting Programs funded by Ministry of Science & Technology of China (No. 2006BAI02A05).
文摘Objective: To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods: Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was administrated intraperitoneally to investigate the impact of SU5416 on tumor angiogenesis and growth in vivo. 32 mice were treated with SU5416 at two different doses every day until the end-point. As a control, 8 mice received no treatment and 8 mice were treated with vehicle (DMSO) only after implantation. Results: Median survival in the treated group was statistically longer compared to that in the control groups (P < 0.05) and no significant systemic adverse was observed. Histological analysis of the treated tumors showed an increase in necroses and reduced in angiogenesis compared to the control tumors. Furthermore, the percent of apoptotic cells increased in the treated tumors by FCM, the expressions of VEGF and KDR had no change after SU5416 administration by western blot. Conclusion: SU5416 may be useful therapeutics drug that specifically inhibits the enzymatic activity of KDR kinase and could down regulate the tumor angiogenesis.
文摘Objective To compare the different effects of endothelia progenitor cells （ EPCs ） or basic fibroblast growth factor （b-FGF） intromyocardial infusion on cardiac function and neovascularization for dilated cardiomyopathy（ DCM） rats. Methods Fifty adult female rats received inguinal subcutaneous injections of isoproterenol （ISO, 250 mg/kg） for induction of DCM. Four weeks later, the model rats were randomly divided into EPCs group, b-FGF group and control group. The 2×106 EPCs （ resolved in 100 μL PBS） , 100 μL b-FGF （ lO0 μg/mL ） and 100 μL PBS were evenly transplanted into the myocardium of EPCs group, b-FGF group and control group, respectively. Three months later, echocardiographic examination and regional myocardial blood flow （RMBF） measurement were performed. EPCs were traced by fluorescence in situ hybridization （FISH）. The protein and mRNA expression of b-FGF in each group was measured by ELISA assay and reverse transcription-polymerase chain reaction （ RT-PCR ） . Results Three months after transplantation, sry positive cells were detected only in EPCs group. The cardiac function as well as RMBF was significantly improved in EPCs group compared with b-FGF group or control group. There was higher capillary density in EPCs group. The protein and mRNA expression of b-FGF was stronger than b-FGF group and control group. Conclusion Transplantation of EPCs can improve cardiac function, induce neovascularization and increase RMBF for DCM rats. The treatment with EPCs has better effect than administration of b-FGF alone.
基金supported by the National Institutes of Health(CA122536 and a minority supplement)the GSU MBD program through a fellowship to SRM
文摘Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.The transcription factor HIF-1 mediates cellular response to hypoxia by promoting processes,such as glycolysis and angiogenesis.Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance.Therefore,HIF-1 is a viable target for cancer therapy.This review summarizes agents that have been described in the literature as HIF-1 inhibitors.The majority of these compounds are indirect inhibitors of HIF-1.
