Protection And Mechanism Of Simvastatin Against The Apoptosis Of MG63 Induced By TNF-a And ActD

[Objective] The aim of the study is to probe the effects of simvastatin on the apoptosis of MG63 induced by TNF-a and Actinomycin D (ActD) and the possible mechanism.[Methods] MG63 cells were cultured with DMEM essential medium supplemented with 10% fetal calf serum and antibiotics. Cell activity was measured by 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium,inner salt(MTs). The pyknotic fragmented nuclei and apoptosis bodies were carefully observed microscopically, and the apoptosis cells were collected to do proteolysis to make sure the accurate pathway by western blotting examination.[Results] The cell activity was not decreased after putting TNF-a alone on MG63 for 24 hours, so was the 10-7-10-9mol/l concentration of simvastatin for 24 hours; in contrast, high concentration of 10-3-10-4mol/l could inhabit the cytogenesis.TNF-a had an obvious cytotoxicity to MG63 cell that was sensitive to ActD, and with the rising in TNF-a concentration,the pyknotic fragmented nuclei and apoptosis bodies were increased.After pre-reserving human osteoblast cell with 10-7-10-9mol/l of simvastatin, then interacted with TNF-a/ActD, and the reduction of the dense segments and apoptosis bodies were demonstrated. The protection related inversingly with the TNF-a concentration.Simvastatin could inhabit the apoptosis of MG63 induced by TNF-a/ActD by means of activating AKT pathway and inhibiting NF-κB pathway。[Conclusions] TNF-a could induce the apoptosis of MG63 sensitive to ActD, and simvastatin could be resistant to the phenomenon. The protection from simvastatin related inversingly with the TNF-a concentration, which primarily by means of activating AKT pathway and inhibiting NF-κB pathway。...