| Objective Human tongue squamous cell carcinoma is one of the most common oral malignant tumors.The study is to investigate the role of 4-o-aminophenol-4’-demethylepipodophyllotoxin ether (ODE) in proliferation, adhesion, migration and invasion of human tongue squamous cell carcinoma cell line Tca8113 and to find effective and specific chemotherapeutics for medical treatment.Methods The effects of ODE on inhibiting proliferation of various cancer cells,including Human hepatoma carcinoma cells HepG2,Human gastric adenocarcinoma cells BGC-823,Human colon carcinoma cells SW480,Human squamous carcinoma cells of the cervix SiHa and Human tongue squamous carcinoma cells Tca8113, were tested by Sulforhodamine B (SRB) assay.The influences of cell cycle and apoptosis in Tca8113 cells were analyzed by Flow Cytometer. Adhesion abilities were tested by cell-matrix adhesion assay. The abilities of migration and invasion were measured by transwell chamber migration assay. The activities of matrix metalloproteinase MMP-2 and MMP-9 were assessed by Gelatin Zymography.Results SRB assay showed that ODE inhibited proliferation of five tumor cells (HepG2, BGC-823, SW480, SiHa, Tca8113) (P<0.05).And ODE significantly inhibited Tca8113 proliferation. There were two effective concentration ranges at which Tca8113 and SW480 cells proliferation was inhibited after treated with ODE. When SW480 cells were treated with ODE at proliferation inhibition range (200,100,50,25,12.5μg/ml)for 72h, IC50 was 23.5 μg/ml; When SW480 cells treated with ODE at other proliferation inhibition range (0.8,0.4,0.2,0.1 μg/ml) for 72h, IC50 was 0.38μg/ml; when Tca8113 cells were treated with ODE at proliferation inhibition range (100,50,25,12.5,6.25,3.125μg/ml) for 72h, IC50 was 16.37μg/ml; when Tca8113 cells were treated with ODE at other proliferation inhibition range (0.8,0.4,0.2,0.1 μg/ml) for 72h, IC50 was 0.12 μg/ml; And at the proliferation inhibition range (100,50,25,12.5 μg/ml), SiHa proliferation was inhibited by ODE, but was not inhibited at the other proliferation inhibition range (0.8,0.4,0.2,0.1μg/ml). Flow cytometry was selected to analyze the influence of cell cycle in Tca8113 cells which treated with ODE for 24h and 48h and at two different range of effective concentrations.The results showed that the cell cycle was arrested at the S phase with the high concentration range. And the cell cycle was arrested at the G2/M phase with low concentration range. In 48h,apoptotic peaks were appeared at the two effective concentration ranges.cell-matrix adhesion assay showed that ODE treatment obviously decreased adhesion abilities of Tca8113 cells on matrigel-coated surface in a dose-dependent manner(.P<0.05). With the concentrations at 100,50,25μg/ml, the adhesion inhibition rates were 72.2%,59.6% and 35.4%, respectively. With the concentrations at 25,12.5,6.25 μg/ml, the migration inhibition rates were 50.8%,33.3% and 12.9%, respectively (P<0.05).With the concentrations at 25,12.5, 6.25μg/ml, the invasion inhibition rates were 90.8%,82.8%,77.9% and 65.6%, respectively(P<0.05). In addition, ODE can inhibit activities of MMP-2 in culture supernatant of Tca8113 cells, but does not show significant inhibition activities on MMP-9.Conclusion ODE inhibited the proliferation of HepG2, BGC-823, SW480, SiHa and Tca8113; ODE significantly inhibited Tca8113 cells. There were two different effective concentration ranges for Tca8113. Tca8113 cells treated with ODE were arrested on different phase——S and G2/M phase under the high and low concentration ranges. And apoptosis of Tca8113 cells was induced by ODE. ODE inhibited matrix adhesion, migration and invasion of Tca8113 cells. ODE influenced the Tca8113 cells’abilities of invasion with inhibiting MMP-2 secretion. |
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