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By Wst In Vitro And In Vivo Efficacy Studies

Posted on:2008-10-23Degree:MasterType:Thesis
Country:ChinaCandidate:H Y YangFull Text:PDF
GTID:2204360242964030Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Background and Aim: Vascular endothelial growth factor (VEGF) or its receptor (VEGFR) has been a new hot spot in cancer therapy study recently which is considered to be an important therapeutic target to angiogenesis. WST is made up of Fc fragment of IgG and the structure of VEGFR-1/Flt-1 and VEGFR-2/KDR which can combine with VEGF. In this research, its effect on tumors and mechanism was studied.Methods: In vitro, the ability of connecting to VEGF was studied with ELISA method, and the effect on HUVEC was studied with CCK-8 method. In vivo, on the foundation of transplantated tumor model including human colon carcinoma (LoVo) and breast cancer (MCF-7) on the nude mice, the effect on tumors were studied with different ways in which some mice were administrated after inoculating tumor cells immediately, others were administrated after the tumors had grown up. Finally, the effect on tumors was studied after WST and chemotherapeutics were administered alliance.Results: WST has a high binding ability to VEGF (Kd is 12.5 PM). This is more powerful than Avastin (Kd is 228.6 PM). WST could inhibit the growth of HUVEC. When its concentration exceed 10nM, its inhibition is obvious (>50%).when its concentration exceed 40nM, its inhibition exceeds 90%. But the inhibition of Avastin is 60% at same concention. So, WST has more excellent effect on HUVEC than Avastin. WST have obvious inhibition to human colon carcinoma (LoVo) and breast cancer (MCF-7). The inhibition relatived to its dose. WST has satisfactory inhibition to tumors not only being administered immediately after inoculating tumor cells, but also after the tumors had grown up. WST has more obvious inhibition than Avastin. The results of histopathologic examination indicated that the effect was relatived to the inhibition of tumor angiogensis and the growth of vascular endothelial cells. The inhibition of WST is stronger than chemotherapeutics, but the inhibition is strongest after they are administered alliance. WST has not effect on the body weigh of animal. Conclusion: WST have obvious effect on tumors. It can obviously inhibit the growth of human colon carcinoma (LoVo) and breast cancer (MCF-7). The inhibition relative with its dose.WST has satisfactory inhibition to tumor not only by administration immediately after inoculating tumor cells, but also by administration after the tumor had grown up. The inhibition.is strongest after WST and chemotherapeutics are co-administration. The effect could relatived with its ability of connecting to VEGF. So, it can inhibit the growth of vascular endothelial cells, angiogensis and tumors. Its biology activity is stronger than Avastin in vitro or in vivo.
Keywords/Search Tags:WST, Tumor, VEGF, HUVEC, Avastin
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