Study On The Anti-tumor Effects And Mechanisms Of DX1002 On Non-Small Cell Lung Cancer

Objective:To investigation the anti-cancer of DX1002 in vitro and in vivo on the non-small cell lung cancer and its mechanism.Methods:1.The anti-proliferation effects of DX1002 were analyzed on 12 cell lines by MTTassay;2.The nude models of A549?NCI-H23?95D non-small cell lung cancer were used to evaluate the anti-cancer effect of DX1002 in vitro,and calculated the tumor inhibition rate of lung cancer;3.Hematoxylin-eosin staining and immunocytochemistry were used to study the preliminary mechanism;4.Cultive human umbilical vein endothelial cell line,experiment of migration?cavity formation?cell apoptosis and necrosis on human umbilical vein endothelial cell to confirmed the mechanism.Result:1.After 72h,DX1002 of experimental drug had a certain inhibitory effect on the growth of 12 human tumor cells,and the IC₅₀ of most solid tumor cells was between 10and 99?M;2.DX1002 has obvious inhibitory effect on three nude mice xenograft human non-small cell lung cancers models,and high?400mg/kg??medium?200mg/kg??low?100mg/kg?three doses of drug have obvious concentration-response relationship,the high dose inhibitory rate was 60%;3.After 4hours,HE staining results showed that the DX1002 and CA4P groups appear internal local tumor tissue necrosis,after24hours,the visible tumor necrosis of large area;PCNA and CD34 of immunohistochemical analysis showed that DX1002 and CA4P group have little impact on the expression of PCNA and CD34 4hours later,PCNA and CD34 expression was observed dropped significantly after 24hours;4.The proliferation inhibitory effect of DX1002 on non-fusion state human umbilical vein endothelial cells?simulated tumor vessels?was significantly stronger than that in the fusion state of human umbilical vein endothelial cells?simulated normal blood vessels?,DX1002 inhibited the activation of vascular endothelial cells and the formation of tube cavity to a certain extent;DX1002has ability to induce necrosis and apoptosis in human non-small cell lung cancer 95D cells.Conclusion:DX1002 of experiment drug had a strong inhibit effect on xenograft tumor of human lung cancer.The influence of DX1002 on the proliferation?mogration and cavrity formation of HUVECs indicates that its anti-tumor effect may be related with the particularity of tumor vessels,which id worthy of further development.