Abstract:Objective To discusses the influence of MG-132 on TRAIL inducing apoptosis of osteosarcoma cell U-2OS.Methods Osteosarcoma cells U-2OS were cultured in 1640 culture medium containing 10%calf serum in a incubator at 37℃and 5%CO2saturation humidity.They were divided into single-use TRAIL group,single-use MG-132 group and combined group.After 24 hours of application of the above-mentioned three dosage regimens,and the apoptotic status of MG-132 cells was detected,the cell inhibition rate was calculated,and the cell changes were observed under light microscope.Results The effect of apoptosis induction in the single-use TRAIL group was not ideal.With the increase of TRAIL concentration,the apoptosis rate of U-2 OS of bone tumor was continuously increased.The apoptosis rate increased with the increase of drug concentration in single-use MG-132 group,and the difference was statistically significant(P<0.05).The apoptotic rate of osteosarcoma cells in combined group,single-use TRAIL group and single-use MG-132 group was significantly higher than that in blank control group,and the difference were statistically significant(P<0.05),and single-use MG-132 group was higher than single-use TRAIL group,and the difference was statistically significant(P<0.05),and the apoptotic rate of osteosarcoma cells in combined group was significantly higher than that in single-use TRAIL group and single-use MG-132 group,and the difference was statistically significant(P<0.05).With the passage of time,the cell inhibition rate increased,and the inhibition rate of combined group was significantly higher than that of single-use TRAIL group and single-use MG-132 group,the maximum value reached at 72 hours([82.32±2.54]%),and the difference was statistically significant(P<0.05).Conclusion Single-use TRAIL can induce apoptosis of osteosarcoma cell U-2 OS,but the effect was not ideal and after combining use of MG-132,it can significantly improve the effect of TRAIL induced apoptosis of U-2 OS.
Ling YH,Liebes L,Zou Y,et al.Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to Bortezomib,a novel proteasome inhibitor,in human H460 non-small cell lung cancer cells[J].J Biol Chem,2003,278(36):33 714-33 723.
Wiley SR,Schooley K,Smolak PJ,et al.Identification and characterization of a new member of the TNF family that induces apoptosis[J].Immunity,1995,3(6):673-682.
[9]
Srivastava RK.TRAIL/Apo-2L:mechanisms and clinical applications in cancer[J].Neoplasia,2001,3(6):535-546.
Pitti RM,Marstem SA,Ruppert S,et al.Induction of apoptosis by Apo22 Ligand,a new member of the tumor necrosis factor cytokine family[J].J Bio Chem,1996,271(22):12 687-12 690.
[12]
EggertA,GrotzerMA,ZuzakTJ,etal.Resistancetotumornecro factor-related apoptosis-inducing ligand(TRAIL)-induced apoptosis in neurobastoma cells correlates with a loss of caspase-8 expression[J].Cancer Res,2001,61(4):1314-1319.
[13]
Shin EC,Ahn JM,Kim CH,et al.IFN-γ induces cell death in human hepatoma cells through a TRAIL/Death receptormediated apoptotic pathway[J].Int J Cancer,2001,93(2):262-268.
[14]
He Q,Huang Y,Sheikh MS.Proteasome inhibitor MG132 up regulates death receptor 5 and cooperates with Apo2-L/TRA-IL to induce apoptosis in Baxp roficient and deficient cells[J].Oncogene,2004,23(14):2254-2558.
[15]
Ciechanover A,Schwartz AL.The ubiquitin system:pathogenesis of human diseases and drug targeting[J].Biochim Biophys Acta,2004,1695(1-3):3-17.
[16]
Carlos Camp s,Vega Iranzo,Roy M Bremnes,et al.Anorexia-Cachexia syndrome in cancer:implications of the ubiquitin-proteasome pathway[J].Support Care Cancer,2006,14(12):1173-1183.
Soldatenkov VA,Dritschilo A.Apoptosis of Ewing′s sarcoma cells is accompanied by accumulation of ubiquitinated proteins[J].Cancer Res,1997,57(18):3881-3885.