Study on the mechanism of zinc oxide nanoparticles inhibiting the cell proliferation,an-giogenesis and lung metastasis of osteosarcoma
Objective:To investigate the effect of zinc oxide nanoparticles on proliferation,angiogenesis and lung metastasis of osteosarcoma in vitro and in vivo.Methods:The SaoS-2 and 143B osteosarcoma cell lines were divided into the experimental group and control group.The experimental group was treated with zinc oxide nanoparticles of dif-ferent concentrations(10 μmol/L,20 μmol/L).After 24 hours,the cell proliferation activity was detected by CCK-8 and clone formation assay,the ability of angiogenesis was detected by tube forming experiment,the expression of VEGF-a protein was detected by Western blot.The growth,lung metastasis and survival of tibial osteosarcoma in vivo were evaluated in nude mouse model,HE staining and immunohistochemistry were used to detect the expression of VEGF-a and Ki-67 protein in tumor tissues.Results:CCK-8 experiment showed that the proliferation inhibi-tion rate of SaoS-2 and 143B osteosarcoma cells in the zinc oxide nanoparticles treatment group was significantly lower than that in the control group from the third day,and showed a time and concentration dependent manner.Clone formation experiment also showed that on the 10th day,the number of cell communities of SaoS-2 and 143B osteosar-coma cells treated with zinc oxide nanoparticles was significantly less than that of the control group.The results of tube forming experiment showed that compared with the control group,zinc oxide nanoparticles could significantly inhibit the angiogenesis of human umbilical vein endothelial cells.Western blot results showed that the expression of VEGF-a protein in osteosarcoma cells treated with zinc oxide nanoparticles was significantly downregulated.The results of in vi-vo model of tibial osteosarcoma in nude mice showed that the zinc oxide nanoparticles treatment group significantly in-hibited the growth of tibial osteosarcoma in situ and lung metastasis,the expression of VEGF-a and Ki-67 proteins in tumor tissue but prolonged the survival time of nude mice.Conclusion:Zinc oxide nanoparticles can inhibit the proliferation,angiogenesis and improve the prognosis,and its mechanism may be related to the downregulation of VEGF-a protein expression.