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http://dx.doi.org/10.7314/APJCP.2014.15.16.6791

Silibinin Inhibits Proliferation, Induces Apoptosis and Causes Cell Cycle Arrest in Human Gastric Cancer MGC803 Cells Via STAT3 Pathway Inhibition  

Wang, Yi-Xin (Department of Pharmacy, Sichuan Cancer Hospital)
Cai, Hong (Department of Pharmacy, Sichuan Cancer Hospital)
Jiang, Gang (Department of Pharmacy, Sichuan Cancer Hospital)
Zhou, Tian-Bao (Ningbo Hospital)
Wu, Hai (Department of Obstetrics and Gynecology, Suining Central Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.16, 2014 , pp. 6791-6798 More about this Journal
Abstract
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 andapoptosis 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.
Keywords
gastric cancer; apoptosis; cell-cycle arrest; STAT3 pathway; silibinin;
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