Inhibitory Effect of Hederasaponin B on Gastric Cancer HGC-27 Cells and Its Mechanism Based on Bioinformatics / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell and the mechanism. MethodMethyl thiazolyl tetrazolium （MTT） assay， hematoxylin-eosin （HE） staining， 4'，6-diamidino-2-phenylindote （DAPI） staining， colony formation assay， scratch assay， and flow cytometry were employed for the analysis of apoptosis and cell cycle. Thereby， the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell was investigated. Then the Pharm Mapper， UniProt， Swissdock， STRING， and Metascape were used for target screening， gene annotation， molecular docking， protein-protein interaction （PPI） network construction， Gene Ontology （GO） term and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis to explore the mechanism. ResultHederasaponin B （15， 30， 60， 120 μmol·L-1） can significantly reduce the survival rate of HGC-27 cell （P<0.01） in a time-dependent and dose-dependent manner compared with the blank group. It had no significant toxicity to normal GES-1 cell at concentration below 120 μmol·L-1. Compared with the blank group， hederasaponin B （30， 60， 120 μmol·L-1） induced cytoplasmic vacuolization， and nuclear deformation and karyopyknosis， inhibited the migration of HGC-27 cell （P<0.01）， and brought about the apoptosis （P<0.05， P<0.01） and cell cycle arrest of HGC-27 cell （P<0.05， P<0.01）. Hederasaponin B （10， 20， 30 μmol·L-1） also suppressed the independent survival ability and proliferation ability of HGC-27 cell （P<0.01）. The possible action targets were kinesin-like protein KIF11， cGMP-specific 3，5 cyclic phosphodiesterase， caspase-3， serine/threonine protein kinase Chk1， proto-oncogene tyrosine protein kinase， epidermal growth factor receptor， and mitogen-activated protein kinase （MAPK） 8. The mechanism may be related to MAPK signaling pathway （pathways in cancer）， adhesion connection， focal adhesion and proteoglycans in cancer （epithelial cell signaling pathways in Helicobacter pylori infection）. ConclusionHederasaponin B exerts significant inhibitory effect on gastric cancer HGC-27 cell through multiple targets and multiple pathways.