Effects Of Podophyllic Acid Piperdyl Nitroxyl Radical Hydrazine On Gastric Cancer Cells And Angiogenesis Factor

Objectives:To study stable nitroxyl radicals spin-labeled podophyllotoxin derivatives-podophyllic acid piperdyl nitroxyl radical hydrazine(GP1) inhibit activities of gastric cancer cells BGC-823、MKN-45in vitro and the mechanism of anti-angiogenesis, providing molecular mechanism and the theoretical basis for further research and development of anti-tumor drugs.Methods:CCK-8assay was used to observe the inhibition rate of gastric carcinoma cells in different concentrations and different time points.The apoptosis were examined through FCM.The invasiveness was examined in Transwell chamber; RT-PCR was used to detect the expressions of VEGF-A VEGFR、Ang-1、Tie2、MMP-2、MMP-9mRNA in the cell lines.Results:1.GP1have the inhibitory effect and the most obvious inhibition when the concentration of it was100μg·mL-1. The inhibition rate of GP1in100μg·ml-1on gastric carcinoma BGC-82324h、48h、72h were31.31%,36.69%,39.23%respectively;on gastri carcinoma MKN-4524h、48h、72hwere64.38%,73.16%,80.32%respectively;2.GP1can induce gastric cancer cell apoptosis,effect increasing the effect with the time.The apoptosis rate of GP1in100μg·mL-1on gastric carcinoma BGC-82324h、48h were0.0800±0.1000%、0.1667±0.01528%; gastric carcinoma MKN-4524h、48h were0.0733±0.02082%、0.2767±0.01202%。3.GP1can inhibit gastric cancer cell migration.The migration rate of GP1in100μg·mL-1on gastric carcinoma BGC-82324h、48h were18.85%、25.15%; gastric carcinoma MKN-4524h、48h were17.29%、24.28%。4.GP1in200、100、50μg·mL-1were inhibited the expression of VEGF-A、 VEGFR、Ang-1、Tie2、MMP-2、MMP-9mRNA.Conclusions:GP1has inhibitory effect on gastric carcinoma cells in vitro by apoptosis-inducing.GPl may inhibit migration of gastric carcinoma cells by inhibiting expression of MMP-2、MMP-9、MRNA. GP1may inhibit angiogenesis of gastric carcinoma cells by inhibiting expression of VEGF-A、VEGFR、Ang-1、Tie2MRNA.