Silibinin improves the cytotoxicity of methotrexate in chemo resistant human rhabdomyosarcoma cell lines.

OBJECTIVE To investigate whether silibinin (SDH) could overcome chemoresistance of methotrexate (MTX)-resistant human rhabdomyosarcoma (hRD). METHODS This study was conducted at the Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq from October 2012 to March 2013. In this in vitro study, resistance to MTX was induced in hRD cell line, the cells were treated with different concentrations of MTX or SDH alone, and in combination. Cell viability was determined by tetrazolium assay. RESULTS The SDH in a concentration-dependent pattern, enhanced the sensitivity of MTX-resistant cells to the maximum cytotoxic concentration of MTX, and decreased the IC50 (concentration resulting in 50% inhibition of cell growth) of MTX by 17.8 fold. The decrease in IC50 of MTX was negatively correlated with increasing SDH concentrations with R2 = 0.78 and p=0.04. CONCLUSION The SDH improves the sensitivity of MTX-resistant hRD cell lines to the cytotoxic activity of MTX in concentration-dependent pattern.