| Background Angiogenesis,the development of new blood vessels from the endothelium of a preexisting vasculature,is an important component of wound healing,embryonic vascular development as well as pathological processes such as tumor growth,diabetic retinopathies.It has been evidenced that angiogenesis is essential for tumor growth,invasion and metastasis.Antiangiogiogensis has been the one of the effective methods of antitumor. As we know,many compounds have proved effective to inhibit the growth of tumor. The mechanization have been mainly realized.Although a wide range of angiogenesis stimulators and inhibitors have been identified,the most of importance is vascular endothelial growth factor(VEGF),which has many biological characters such as inducing endothelial cell proliferation.VEGF expression is associated with tumor blood growth,and tumor can be inhibited by suppressing VEGF expression. Objectives This study was initiated to determined whether sodium ferulate and total glucosides of pacony inhibit angiogenesis of H22 tumor growing in the mice and to explore its action mechanism,which could give a preliminary experimental basis for antiangiogenesis of Traditional Chinese Drug for promoting Blood circulation to remove blood stasis. Methods Chapter 1 Animal Studies Cells of the tumor H22 were jnjected s.c. into the right flanks(2×106/ml ). Animals were randomized for therapy on the second day and treated with sodium ferulate 200,100,50mg/kg/d , total glucosides of pacony 200,100,50mg/kg/d as well as sodium as control group for 14 days.Then,the volume,weight,tumor microvessel density were determinated. Chapter 2 Endothelial and Tumor Cell Proliferation Assay Vascular endothelial cells(ECV304) and H22 cells. Cells were incubated with sodium ferulate in various concentrations, the number of metabolically active cells was determined by MTT assay and calculate IC50,and then it was investigated whether the tumor cells deduced vascular endothelial cells proliferating can be inhibited by SF . Chapter 3 RT-PCR RT-PCR was employed to assay the expression of VEGF mRNA in mice tumor treated with various concentrations of sodium ferulate. Results Treatments with total glucosides of pacony in any concentrations were ineffective on mice tumor growth.In contrast,injections of sodium ferulate reduced tumor volume significantly(p<0.05). Immunohistochemical analysis revealed that treatment with sodium ferulate inhibited expression of VEGF(p<0.05),leading to a decrease in microvessel density,which also decreased the staining of proliferating cell nuclear antigen within tumor.In addition,it can not be proved that the groups treated with total glucosides of pacony are different significantly compared with control group. In vitro,sodium ferulate did not inhibt the proliferation of vascular endothelial cells and H22 tumor cells.However, the ability of H22 tumor cells deducing the proliferation of vascular endothelial cells can be reduced by sodium ferulate(p<0.05).And the IC50 is 18.34μg/ml. The expression of VEGF gene was inhibited obviously by sodiumferulate(p<0.05). Conclusions Total glucosides of pacony can not inhibit the growth of H22 tumor,angiogenesis as well as the expression of VEGF. Sodium ferulate can inhibited the expression of VEGF mRNA and angiogenesis in tumor,which leading to suppressing the growth of tumor in mice. Sodium ferulate can not inhibit the proliferation of vascular endothelial cell and H22 tumor cell directly,its ability of inhibiting of tumor growth depend on reducing the expression of VEGF. Sodium ferulate can decrease the ability of tumor cell deducing the proliferation of vascular endothelail cell. Innovation and significance We first report sodium ferulate can inhibit the growth of tumor,and give the preliminary mechanism that Sodium Ferulate take effect by the means of antiangiogenesis caused by expression of VEGF being suppressed.This study enlarges the pharmacological effect of sodium ferulate and gives the expremental basis for its clinical applications of a...
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