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.