Effect of Smac on TRAIL-induced Apoptosis of Prostate Cancer Cell Line PC-3 and the Molecular Mechanism
- Author:
- No author available
- Issue:
- 2
- DOI:
- 10.1007/s11596-012-0041-7
- Key Word:
- Smac gene;prostate carcinoma;TRAIL;apoptosis
Abstract： The effect of Smac gene on the TRAIL-induced apoptosis of the prostate cancer cell line PC-3 and the molecular mechanism were investigated.The Smac gene was transfected into PC-3 cells under the induction of liposome.The intrinsic Smac gene expression was detected by Western blotting.After treatment with TRAIL as an apoptosis inducer,in vitro cell growth activity was assayed by MTT colorimetry.The apoptosis rate of PC-3 cells was determined by annexin V -FITC and propidium iodide staining flow cytometry.The expression of cellular XIAP and caspase-3 genes was examined by Western blotting.Smac-transfected cells (PC-3/Smac group) had significantly increased Smac protein level as compared with PC-3 controls (P＜0.01).After induction with 100-200 ng/mL TRAIL for 12-36 h,cellular proliferation rate in PC-3/Smac group was significantly lower than in PC-3 controls (P＜0.05).After induction with 100 ng/mL TRAIL for 24 h,the apoptosis rate in PC-3/Smac group was significantly enhanced as compared with that of PC-3 controls (P＜0.05).Accordingly,the XIAP expression level was down-regulated significantly (P＜0.05) and caspase-3 subunit P20 was up-regulated significantly (P＜0.05).It is suggested that the over-expression of cellular Smac can inhibit inhibitor of apoptosis proteins (IAPs),enhance caspases activity and the apoptosis rate of PC-3 cells induced by TRAIL,which may provide a useful experimental basis for prostate cancer therapy.
- [1]Li-Duan Zheng,Qiang-Song Tong,LIANG Wang,etc.Stable transfection of extrinsic Smac gene enhances apoptosis-inducing effects of chemotherapeutic drugs on gastric cancer cells[J].2005,(1).
- [2]Conradt, B..Genetic control of programmed cell death during animal development.[J].2009,2009(1).
- [3]Kaufmann SH,Heldebrant MP,Chiorean MV,etc.Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ.[J].2002,277(46).
- [4]I, Tamm,S M, Kornblau,H, Segall,etc.Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias.[J].2000,6(5).
- [5]Watson RW,Fitzpatrick JM,O'Neill AJ,etc.Inhibitors of apoptosis proteins in prostate cancer cell lines.[J].2002,51(2).
- [6]Pai RC,Leung S,Koeppen H,etc.Safety and antitumor activity of recombinant soluble Apo2 ligand.[J].1999,104(2).
- [7]M, Jo,T H, Kim,D W, Seol,etc.Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand.[J].2000,6(5).
- [8]Adrain C,Creagh EM,Martin SJ.Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2.[J].2001,20(23).
- [9]Wang, C. X.,Youle, R. J..The role of mitochondria in apoptosis.[J].2009,2009(1).
- [10]Subrata, Ray,Alex, Almasan.Apoptosis induction in prostate cancer cells and xenografts by combined treatment with Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand and CPT-11.[J].2003,63(15).
- [11]C B, Thompson.Apoptosis in the pathogenesis and treatment of disease.[J].1995,267(5203).
- [12]Von-Haefen C,Janicke R,Radetzki S,etc.Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance.[J].2001,20(22).
- [13]Alnemri ES,Jia L,Patwari Y,etc.Role of Smac in human leukaemic cell apoptosis and proliferation.[J].2003,22(11).
- [14]Wick W,Weller M,Debatin KM,etc.Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo.[J].2002,8(8).
- [15]G S, Salvesen,V M, Dixit.Caspases: intracellular signaling by proteolysis.[J].1997,91(4).