The Mechanism Of Mzs-1 Inducing Apoptosis Of Human Gastric Cancer Cells Via Inhibiting DNA Topoisomerase Ⅰ

Objective: To investigate whether Mzs-1,a novel lignan compound suppresses the growth and induces apoptosis in human gastric cancer SGC-7901 cell line,and explore the mechanism of Mzs-1 inducing apoptosis in gastric cancer cells.Methods: Human gastric cancer SGC-7901 cells cultured were treated with various concentration of Mzs-1.The antiproliferative effects of Mzs-1 on SGC-7901 cells were measured with CCK-8 assay,and half maximal(50%)inhibitory concentration(IC50)values were calculated.The morphological changes after Mzs-1 treatment of SGC-7901 cells were observed by the inverted microscope.The effects of Mzs-1 on migration capacity were observed by cell scratch test.The cell cycle and apoptotic rate were analyzed by flow cytometry with PI staining.The effect of Mzs-1 on Topoisomerase I(TopoⅠ)activity was studied by using the agarose gel electrophoresis method.The mRNA expression level of TopoⅠ was determined by RT-q PCR.The protein expression of TopoⅠ was detected by Western Blot.Results: Mzs-1 inhibited the viability of SGC-7901 cells,with time-and dose-dependent manner.The IC50 value of Mzs-1 on SGC-7901 cells was38.56μg/ml.Mzs-1 induced SGC-7901 cells morphologic changes with the increasing concentration of Mzs-1 under inverted microscope.The migration ability of SGC-7901 cells was significantly inhibited by Mzs-1.The rate of the apoptosis cells and G2/M phase cells raised significantly after 48 hours treatment with Mzs-1.The results of agarose gel electrophoresis showed that Mzs-1 had significant inhibition of TopoⅠ activity.The expression of TopoⅠ mRNA on SGC-7901 cells decreased with the increasing of Mzs-1 concentration.The protein expression level of TopoⅠ on SGC-7901 cells decreased significantly with the increasing concentration of Mzs-1.Conclusion: Mzs-1 possesses the effects of inhibition of cell viability in human gastric cancer SGC-7901 cell line.Mzs-1 could inhibit the proliferation of SGC-7901 cells and induce apoptosis by arresting cells at G2/M phase in vitro.The mechanisms were related to the decrease of TopoⅠ expression.