Study On Pharmacokinetics Of Resveratrol In Tumor-bearing Mice And Its Suppression Of Angiogenesis

Part1Study on Pharmacokinetics of Resveratrol in Tumor-Bearing MiceObjective: Preliminary study pharmacokinetic characteristics Resveratrol (Res) in C57Bl micebearing melanoma, to provide experimental evidence and theoretical guidance for furtherdevelopment and clinical application of Res. Methods: Tumor-bearing mouse model wasestablished through inoculating B16F10mouse melanoma cells back subcutaneously. Reslow dose group single dose, blood collection at different time points orbital venous plexus,the application of high performance liquid chromatography-mass spectrometry(HPLC-MS/MS) analysis to detect plasma Res concentration using a DAS ver2.2pharmacokinetic of procedures to deal with the experimental data. Results: Successfullyestablish mouse melanoma B16F10subcutaneous xenograft model,100%of the rate oftumor formation. Eating, drinking and activity of the tumor-bearing mice were under goodcondition. AUC0-t56.773±18.508μ g/(L h), AUC0-∞113.547±43.135μ g/(L h), Tmax0.167±0.034h, Cmax5752.327±578.272μ g/L, apparent volume of distribution Vd424.932±132.827L/kg, half-life t1/22.228±0.934h, clearance CL1761.391±323.425L/(h kg).Conclusion: This study explicitly Res pharmacokinetic characteristics in Dutch melanoma inmice. Part2Effect of Resveratrol on Angiogenesis in Tumor-Bearing miceObjective: To provide experimental evidence and theoretical guidance for furtherdevelopment and clinical application of Res, study effect and mechanism of mouse melanoma vascular generated by Res. Methods: These animals were randomly divided intoblank group、Res low-dose group、Res high dose group and dacarbazine group, each was12,inoculation administration after three days: blank group, normal feeding, ig.CMC-Na10mL/(kg d）; Res high dose group, ig.100mg/(kg d); the Res the low-dose group,ig.50mg/(kg d); dacarbazine group ip.40mg/(kg3d). The above groups were administratedcontinuously for3weeks. The regularly observed tumor growth and tumor-bearing miceweight change. Sacrifice tumor-bearing mice after the last administration with collectingtumor tissues. Weigh tumor weight inhibitory rate was calculated. HE staining of tumortissue sections was observed about the morphological changes. Detection of CD34microvessel density and tumor tissue expression of MMP-2protein detection were done byimmunohistochemical. Use Western blotting to detect the expression of VEGF protein intumor tissue. Results: Eating, drinking and activity of the tumor-bearing mice were undergood condition.21days after continuous administration of the Res group of low-dose, highdose Res group and positive drug group inhibition rates were17.47％、40.98％and72.66％, respectively. The average tumor weight of each dose group was significantly lowerthan the control group. HE staining were observed visible in all the different sizes of thenecrotic area of the necrotic area Res group of low-dose, high-dose Res group and positivedrug group compared to the control group mice tumor tissue. Microvessel density in eachdose group was significantly lower than the control group. The protein expression of MMP-2in each dose group was significantly less than the control group. VEGF protein expressionwas significantly less than the control group in each dose group. Conclusion: This studyfound that Res could effectively inhibit angiogenesis mouse melanoma through loweringthe MVD, MMP-2and VEGF expression.