To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a humanembryonic kidney-293 cell model using vascular endothelial growth factor (VEGF) gene promoter as the drug t...To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a humanembryonic kidney-293 cell model using vascular endothelial growth factor (VEGF) gene promoter as the drug target. Inthis model, VEGF gene promoter may regulate the expression of the luciferase reporter gene by responding to thestimulation of drug molecules. This cell model allows rapid and efficient screening of vascular-inducing activecomponents from several drug monomer molecules. Furthermore, we used rat bone marrow mesenchymal stem cells(rMSCs) to conduct a preliminary study on the activity of alantolactone. Using simvastatin as a positive control, weinvestigated the effects of alantolactone on the expression of vascular-related cell marker molecules such as VEGF andα-smooth muscle actin (α-SMA) in rMSCs. According to our results, 0.1, 1, 3 and 5 μM of alantolactone upregulated thetranscriptional luciferase gene activity of VEGF promoter, and a significant difference from that in the control group wasobserved. Among them, 3μM of alantolactone showed the better effect than that of 3 μM of simvastatin (P = 0.036) andother concentrations of alantolactone and simvastatin showed similar effects. Compared with that in the control group,rMSCs induced with 1μM alantolactone for 3 days showed a significant increase in the relative mRNA expressions ofVEGF and α-SMA genes. However, these effect of 5 μM alantolactone were weaker than those of 5 μM simvastatin (P 〈0.05); rMSCs treated with 1 μM alantolactone for 3 days showed brighter green fluorescence (FITC marker) of α-SMAand VEGF in situ expression than that observed in the control group and similar fluorescence intensity than that ofsimvastatin group in an immunoradiometric assay. The above results demonstrate the reliability of the highly efficientsystem for screening of active drug molecules and confirmed the vascular induction function of alantolactone at the geneand protein levels.展开更多
Researches have shown that cancer stem cells, regulated by the niche where they reside, are the roots of oncogenesis, relapse and metastasis. To date, very few treatments have targeted on cancer stem cells. The author...Researches have shown that cancer stem cells, regulated by the niche where they reside, are the roots of oncogenesis, relapse and metastasis. To date, very few treatments have targeted on cancer stem cells. The authors study that the regulated factors in the niche share the characteristics of yin-yang in the theory of traditional Chinese medicine, which has confirmed its therapeutic effects in the prevention and treatment of cancer. So the authors presume that the mechanisms of traditional Chinese medicine on the prevention and treatment of cancer may be related to the yin-yang balance of the niche of cancer stem cells.展开更多
文摘To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a humanembryonic kidney-293 cell model using vascular endothelial growth factor (VEGF) gene promoter as the drug target. Inthis model, VEGF gene promoter may regulate the expression of the luciferase reporter gene by responding to thestimulation of drug molecules. This cell model allows rapid and efficient screening of vascular-inducing activecomponents from several drug monomer molecules. Furthermore, we used rat bone marrow mesenchymal stem cells(rMSCs) to conduct a preliminary study on the activity of alantolactone. Using simvastatin as a positive control, weinvestigated the effects of alantolactone on the expression of vascular-related cell marker molecules such as VEGF andα-smooth muscle actin (α-SMA) in rMSCs. According to our results, 0.1, 1, 3 and 5 μM of alantolactone upregulated thetranscriptional luciferase gene activity of VEGF promoter, and a significant difference from that in the control group wasobserved. Among them, 3μM of alantolactone showed the better effect than that of 3 μM of simvastatin (P = 0.036) andother concentrations of alantolactone and simvastatin showed similar effects. Compared with that in the control group,rMSCs induced with 1μM alantolactone for 3 days showed a significant increase in the relative mRNA expressions ofVEGF and α-SMA genes. However, these effect of 5 μM alantolactone were weaker than those of 5 μM simvastatin (P 〈0.05); rMSCs treated with 1 μM alantolactone for 3 days showed brighter green fluorescence (FITC marker) of α-SMAand VEGF in situ expression than that observed in the control group and similar fluorescence intensity than that ofsimvastatin group in an immunoradiometric assay. The above results demonstrate the reliability of the highly efficientsystem for screening of active drug molecules and confirmed the vascular induction function of alantolactone at the geneand protein levels.
基金supported by grants from the National Nature Science Foundation of China and No.2006BAI04A05 from the Eleventh Five-Year Program of the National Science and Technology Project (No.30772867)
文摘Researches have shown that cancer stem cells, regulated by the niche where they reside, are the roots of oncogenesis, relapse and metastasis. To date, very few treatments have targeted on cancer stem cells. The authors study that the regulated factors in the niche share the characteristics of yin-yang in the theory of traditional Chinese medicine, which has confirmed its therapeutic effects in the prevention and treatment of cancer. So the authors presume that the mechanisms of traditional Chinese medicine on the prevention and treatment of cancer may be related to the yin-yang balance of the niche of cancer stem cells.