An Experimental Study On The Effect Of Arsenic Trioxide On U2-OS In Human Osteosarcoma Cells

Background and purposesOsteosarcoma is the most common primary bone tumor in children and young adults, with high ability of invasion and high recurrence after operation. Arsenic trioxide (arsenic trioxide As2O3) is one of effective ingredients of the white arsenic(a traditional Chinese medicine). It is well known as an effective treatment for acute promyelocytic leukemia in the 70s last century and received great attention at that time and was used to treat other malignant tumor afterwards. So, in order to explore the effects of arsenic trioxide on human osteosarcoma cells, we observe in vitro the effects of arsenic trioxide on the morphology, proliferation, cycle and apoptosis of osteosarcoma U2-OS in different concentration and at different time point.Materials and methodsArsenic trioxide in different concentration(0.5,1,1.5,μmol/L) effect on human osteosarcoma cells,15mg/L 5-fluorouracil (5-FU) as positive control, The negative control group was be added nutrient of the same volume medium, we use four methyl thiazolyl tetrazolium salt (MTT) to detect the cell proliferation rate. Cell cycle and apoptosis rate tested by the Flow cytometry(FCM). cell morphology was observed by the cell immunofluorescence staining.ResultsThe arsenic trioxide effect U2-OS cell nuclei pyknosis, appearance, cells dyeing deepen, apoptotic body in different concentration and at different time point; Arsenic trioxide can make U2-OS cells apoptosis and control cell proliferation, early apoptosis rate, blank group 1.2%,0.5 u mol/L group was 23.6%,1 mol/L group was 39.1%,1.5 mol/L group was 51%. Arsenic trioxide can make U2-OS cell to be arrested in S phase, and in G0/G1 phase of the partial cell, so the cell is blocked in the active stage S, the avil is controled the tumor cell proliferation.1. Arsenic trioxide has an inhibitory effect on the proliferation of U2-OS cell.2. Study shows that arsenic trioxide can block some U2-OS cells in S phase, some in G0/G1 phase and this is closely correlated with its concentrations. This also indicates that the effect of arsenic trioxide depends on the concentration.3. The results indicate that arsenic trioxide (0.5～1.5 mol/L) can significantly induce apoptotic body morphological changes of U2-OS cells.4. Flow cytometric detection shows that apoptosis rate has positive correlation with the concentrations and treatment time of arsenic trioxide, which suggests that arsenic trioxide can effectively induce the apoptosis of U2-OS cells. These results demonstrate that the inhibitory effect of arsenic trioxide on U2-OS cell proliferation is mainly implemented via inducing U2-OS cell apoptosis, providing a theoretical basis for clinical work.