Silibinin inhibits proliferation, induces apoptosis and causes cell cycle arrest in human gastric cancer MGC803 cells via STAT3 pathway inhibition

Asian Pac J Cancer Prev. 2014;15(16):6791-8. doi: 10.7314/apjcp.2014.15.16.6791.


Background: To investigate the effect of silibinin on proliferation and apoptosis in human gastric cancer cell line MGC803 and its possible mechanisms.

Materials and methods: Human gastric cancer cell line MGC803 cells were treated with various concentration of silibinin. Cellular viability was assessed by CCK-8 assay and apoptosis and cell cycle distribution by flow cytometry. Protein expression and mRNA of STAT3, and cell cycle and apoptosis regulated genes were detected by Western blotting and real-time polymerase chain reaction, respectively.

Results: Silibinin inhibits growth of MGC803 cells in a dose- and time-dependent manner. Silibinin effectively induces apoptosis of MGC803 cells and arrests MGC803 cells in the G2/M phase of the cell cycle, while decreasing the protein expression of p-STAT3, and of STAT3 downstream target genes including Mcl-1, Bcl-xL, survivin at both protein and mRNA levels. In addition, silibinin caused an increase in caspase 3 and caspase 9 protein as well as mRNA levels. Silibinin caused G2/M phage arrest accompanied by a decrease in CDK1 and Cyclin B1 at protein and mRNA levels..

Conclusions: These results suggest that silibinin inhibits the proliferation of MGC803 cells, and it induces apoptosis and causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9, potentially via the STAT3 pathway.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • CDC2 Protein Kinase
  • Caspase 3 / biosynthesis
  • Caspase 3 / genetics
  • Caspase 9 / biosynthesis
  • Caspase 9 / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin B1 / biosynthesis
  • Cyclin B1 / genetics
  • Cyclin-Dependent Kinases / biosynthesis
  • Cyclin-Dependent Kinases / genetics
  • Down-Regulation
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis
  • Inhibitor of Apoptosis Proteins / genetics
  • M Phase Cell Cycle Checkpoints / drug effects
  • Myeloid Cell Leukemia Sequence 1 Protein / biosynthesis
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • RNA, Messenger / biosynthesis
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / biosynthesis
  • Silybin
  • Silymarin / pharmacology*
  • Stomach Neoplasms / drug therapy*
  • Survivin
  • bcl-X Protein / biosynthesis
  • bcl-X Protein / genetics


  • Antineoplastic Agents
  • BCL2L1 protein, human
  • BIRC5 protein, human
  • CCNB1 protein, human
  • Cyclin B1
  • Inhibitor of Apoptosis Proteins
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • RNA, Messenger
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Silymarin
  • Survivin
  • bcl-X Protein
  • Silybin
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases
  • Caspase 3
  • Caspase 9