Effect of Silymarin on Expression of micro-RNA-21 and Matrix Metalloproteinase (MMP) 2 and 9 and Tissue Inhibitors of Matrix Metalloproteinase (TIMP) 1 and 2 in Hepatocellular Carcinoma Cell Line (HepG2).

BACKGROUND

Silymarin is a flavonolignan that has various medicinal properties such as liver protection, antioxidant, anti-inflammatory, anti-cancer and heart protection activities. The aim of this study was to investigate the effect of silymarin on the expression level of , matrix metalloproteinase(), and their tissue inhibitors () in liver cancer HepG2 cell line.

METHODS

An experimental study was conducted on the human HepG2 cells prepared from Pasteur Institute, Tehran, Iran. Four concentrations of 0 (control), 50, 100, and 150 µM of silymarin were considered as the study groups according to the MTT assay. Gene expression study was performed using real-time PCR. The studied genes were , , , and . In addition, some apoptosis-related genes including , and () were investigated. was used as an internal control. Relative expression was calculated by REST program using t-test on the logarithm of expression considering a significance level of 0.05.

RESULTS

The significant up-regulations consisted of genes for doses 100 µM and 150 µM, and the apoptosis activating genes and ( < 0.05). The significant down-regulations consisted of in all concentrations, 2 in concentration 100 µM, and the apoptosis inhibitory gene in concentrations 50 µM and 100 µM ( < 0.05). In addition, as an oncogenic micro-RNA showed significant down-regulation for all doses ( < 0.05). All the comparisons were with the control group.

CONCLUSION

The present study showed that silymarin could affect the HepG2 cell line at the gene expression level increasing apoptosis and changing the expression of , , , and . These findings were in line with each other and in favor of suppression of tumoral activity in this cell line.