Hederagenin Induces The Apoptosis Of Gastric Cancer Cells Via Mitochondria-mediated Pathway

Objective To investigate the anti-tumor activity of hederagenin(HG)on gastric cancer cells in vitro and in vivo,and clarify the mechanism from the sight of mitochondria-mediated apoptosis pathway.Methods In vitro experiment: the MTT method and colony formation assay were used to detect the anti-proliferation activity of HG on MGC803 and SGC7901 gastric cancer cells;wound healing assay and cell migration assay were used to detect the effect of HG on the cell migration ability of MGC803 and SGC7901 gastric cancer cells;transwell assay was used to detect the effect of HG on the invasion ability of MGC803 and SGC7901 gastric cancer cells;flow cytometry was used to detect the apoptosis of MGC803 and SGC7901 gastric cancer cells after HG treatment;mitochondria stainning and mitochondrial membrane potential(MMP)detection were used to evaluate the functions of mitochondria after HG treatment;intracellular ROS level was detected after HG treatment;western blotting was used to detect the expression of mitochondrial mediated apoptosis and PI3K/Akt pathway related proteins level after HG treatment.In vivo experiment: nude mice xenografts model were used to investigate the anti-cancer activity of HG in vivo;hematoxylin-eosin(HE)staining was used to evaluate the effect of HG on the morphology of tumor tissue;immunofluorescent staining(IHC)was used to evaluate the expression of ki-67.Results In vitro experiment: HG could significantly reduce the viability,inhibit the growth,weaken the migration ability and reduce invasion ability of MGC803 and SGC7901 gastric cancer cells in a dose dependent way;HG could induce apoptosis of SGC7901 and MGC803 gastric cancer cells in a dose dependent way;HG could induce the apoptosis of gastric cancer cells via mitochondria-mediated pathway;HG could modulate the expression of mitochondrial mediated apoptosis and PI3K/Akt pathway related proteins in SGC7901 and MGC803 gastric cancer cell.In vivo experiment: compared with model control group,HG could significantly inhibit the tumor growth in a dose dependent way;HG could inhibit the tumor growth by inhibiting the proliferation of gastric cancer cells.Conclusion HG could inhibit the occurrence and development of gastric cancer by regulating the ROS and PI3K/AKT pathways and promoting mitochondrial mediated apoptosis.