Genistein Suppression of Matrix Metalloproteinase 2 (MMP-2) and Vascular Endothelial Growth Factor (VEGF) Expression in Mesenchymal Stem Cell Like Cells Isolated from High and Low Grade Gliomas

摘要

Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.