Abstract OBJECTIVE: The aim of this study was to investigate whether the induction of caspase-8 by γ-interferon (IFNγ) renders neuroblastoma (NB) cells sensitive to tumor necrosis factor related apoptosis inducing ligand(TRAIL). METHODS: Caspase-8 mRNA expression was determined by RT-PCR. The effects of IFNγ, TRAIL, IFNγ +TRAIL and caspase-8 inhibitor+ TRAIL on the growth and apoptosis of NB cells were detected with the methods of reduction rate of Alamar Blue assay and flow cytometry. The relative caspase-8 activity was measured with colorimetric assay. RESULTS: Caspase-8 expression was detectable in CHP212 cells which were sensitive to TRAIL, with an increased expression after treatment with IFNγ. Caspase-8 was undetectable in SH-SY5Y(SY5Y) cells which were resistant to TRAIL, but an increased expression of caspase-8 mRNA was found after treatment with IFNγ. Moreover, TRAIL combined with IFNγ induced apoptosis in SY5Y cells. The relative caspase-8 activity of CHP212 cells increased with the prolonged TRAIL action time. The relative caspase-8 activity of SY5Y cells in the IFNγ+TRAIL group was significantly higher than those of the control, IFNγ, TRAIL and inhibitor groups. CONCLUSIONS: NB cells expressing caspase-8 are sensitive to TRAIL. TRAIL induces apoptosis in NB cells with an increase of relative caspase-8 activity.［Chin J Contemp Pediatr, 2010, 12 (11):902-907］
TONG Hai-Xia,LU Chun-Wei,WANG Li-Wei et al. Role of caspase-8 in TRAIL-induced apoptosis of neuroblastoma cell lines[J]. 中国当代儿科杂志, 2010, 12(11): 902-907.
TONG Hai-Xia,LU Chun-Wei,WANG Li-Wei et al. Role of caspase-8 in TRAIL-induced apoptosis of neuroblastoma cell lines[J]. CJCP, 2010, 12(11): 902-907.
［1］Griffith TS, Anderson RD, Davidson BL, Williams R, Ratliff TL. Adenoviralmediated transfer of the TNF-related apoptosis-inducing ligand/Apo-2 ligand gene induces tumor cell apoptosis［J］. J Immunol , 2000, 165（5）: 2886-2894.
［2］Johnsen J, Pettersen I, Ponthan F, Sveinbjornsson B, Flaegstad T, Kogner P. Synergistic induction of apoptosis in neuroblastoma cells using a combination of cytostatic drugs with interfern-γ and TRAIL［J］. Int J Oncol, 2004, 25(6): 1849-1857.
［3］Tong HX, Lu CW, Zhang JH, Ma L, Zhang JH. Combination of γ-interferon with TRAIL and cisplatin or etoposide induces apoptosis in neuroblastoma cell line SH-SY5Y［J］. Chin Med Sci J, 2007, 22(1): 38-43.
［4］Tong HX, Lu CW, Zhang JH, Zhang JH. Enhanced effect of IFNγ on the induced-apoptosis of neuroblastoma cells by cytotoxic drugs［J］. Pediatr Hemat Oncol, 2008, 25(6):549-558.
［5］Tong HX, Lu CW, Yang YM, Zhang JH, Zhang JH. Role of caspase-8 as a determinant in TRAIL sensitivity of neuroblastoma cell lines［J］. Pediatr Hemat Oncol, 2009, 26(8):549-559.
［6］Yang X, Merchant MS, Romero ME, Tsokos M, Wexler LH, Kontny U, et al. Induction of caspase-8 by interferon gamma renders some neuroblastoma cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but reveals that a lack of membrane TR1/ TR2 also contributes to TRAIL resistance in NB［J］. Cancer Res, 2003, 63(5):1122-1129.
［7］Fulda S, Debatin KM. 5-Aza-2′-deoxycytidine and IFN-gamma cooperate to sensitize for TRAIL-induced apoptosis by upregulating caspase-8［J］. Oncogene, 2006, 25(37):5125-5133.
［8］Liedtke C, Groger N, Manns MP, Trautwein C. Interferon-alpha enhances TRAIL-mediated apoptosis by up-regulating caspase-8 transcription in human hepatoma cells［J］. J Hepatol, 2006, 44(2):342-349.
［10］Kim YH, Lee YJ.Time sequence of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cisplatin treatment is responsible for a complex pattern of synergistic cytotoxicity［J］. J Cell Biochem, 2006, 98(5):1284-1295.
