Protective effect of silymarin against rapamycininduced apoptosis and proliferation inhibition in endothelial progenitor cells

AIM:To study the effect of rapamycin on proliferation and migration of endothelial progenitor cells (EPCs) and to observe the protective effect of silymarin on EPCs under rapamycin intervention. METHODS: Peripheral blood was collected from human volunteers. Mononuclear cells (MNCs) were separated by density centrifugation and were induced to differentiate into EPCs in vitro. EPCs were intervened with different concentrations of rapamycin (0, 0.1, 1, 10, 100 ng/ml) for 24 h and different times (0, 6, 12, 24, 48 h) and proliferation and migration of EPCs were then detected. EPCs were intervened with different concentrations of silymarin (0, 25, 50, 100 μg/ml) for 24 h and proliferation, migration and apoptosis of EPCs were then detected. Rapamycin (1 ng/ml) and silymarin (25, 50, 100 μg/ml) were added in EPCs for 24 h and proliferation, migration, apoptosis and angiogenesis were then detected. RESULTS: Compared with those in the control group, rapamycin (1, 10, 100 ng/ml) inhibited proliferation and migration of EPCs in a concentration and timedependent manner (P<005). Silymarin (50, 100 μg/ml) enhanced proliferation and migration of EPCs and inhibition of apoptosis in a concentrationdependent manner (P<005). After adding rapamycin (1 ng/ml) and silymarin (25, 50, 100 μg/ml) for 24 h, silymarin inhibited the proapoptotic effect of rapamycin on EPCs and reversed the inhibitive effect of rapamycin on proliferation, migration and angiogenesis of EPCs (P<005). CONCLUSION: Rapamycin inhibits proliferation and migration of EPCs in a concentration and timedependent manner. Silymarin enhances proliferation and migration of EPCs and inhibition of apoptosis in a concentrationdependent manner. Silymarin also inhibits the proapoptotic effect of rapamycin on EPCs and reverses the inhibitive effect of rapamycin on proliferation, migration and angiogenesis of EPCs.