| Our study is the preliminary research of drug loaded cement for the local treatment of osteosarcoma. Cytotoxicity studies including observation of cell size, shape, proliferation, division, migration, adhesion, death and apoptosis were employed, to investigate the inhibition effects of arsenic trioxide(Arsenic Trioxide, As2O3) on inhibition osteosarcoma MG63 cells and determine the effective dosage; to study the synergistic effects of ascorbic acid(ascorbic acid, AA) and As2O3 on inhibition MG63 cells, and determine the optimal dosage; to provide evidence for the synergistic effects of AA and As2O3 on inhibition MG63 cells using ChIP-on-chip method and PCR confirmation.Part1 Experimental study on the synergistic effects of ascorbic acid and arsenic trioxide on inhibition of osteosarcoma MG63 cells in vitroObjective:To investigate the synergistic effects of AA and As2O3 on the inhibition of osteosarcoma MG63 cell lines in vitro.Methods:The osteosarcoma MG63 cells were treated with AA (62.5uM), arsenic trioxide (1μM) and As2O3 (62.5μmol/L) plus As2O3 (1μM) respectively. The Cell-IQ (continuous live cell imaging and analysis platform, Cell IQ) was used to observe the cell proliferation and morphologic changes of MG-63 cells.Results:The proliferation inhibition and apoptosis of MG63 cells were obsetved when treated with AA (62.5μM) and As2O3 (1μM) independently. The proliferation inhibition and apoptosis were more obvious in the MG63 cells treated by AA (62.5μM) combined with As2O3 (1μM).Conclusions:The AA and As2O3 had synergistic effects on the proliferation inhibition and apoptosis of MG63 cells. Our studies provide new pathway and experimental evidence for the clinical treatment of osteosarcoma.Part 2 The mechanism of synergistic effects of ascorbic acid and arsenic trioxide on inhibition of osteosarcoma MG63 cellsObjective:To investigate the mechanism of synergistic effects of AA and As2O3 on inhibition of osteosarcoma MG63 cells.Methods:Human (MG63) osteoblast cell lines were treated with AA and As2O3, and the effects of drug-drug interaction on the transcriptome were investigated. Firstly, the mixed linear model was employed to simulate the interaction between AA and As2O3, and the gene set was confirmed. Secondly, the gene expression profiles of MG63 cells treated by mono- or mixed drug were studied using singular value decomposition analysis. Different modes of gene expression for drug interactions were founded among the gene expression files. And the transcriptional regulatory networks were analyzed for characterizing global gene expression profiles. Further, the functional relevance of gene for synergistic interaction on MG63 cells were employed using gene ontology and signaling pathway.Results:The transcriptome of MG63 cell lines treated by AA, As2O3 and AA plus As2O3 were identified in two different ways. And the functional relevance of gene sets was also investigated.Conclusions:Ours studies suggested the possible mechanism of synergistic effects of AA and As2O3 on inhibition of osteosarcoma MG63 cells. |
PDF Full Text Request