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IFN γ enhances the anti tumor effect of TRAIL against giant cell tumor of bone in vitro
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Abstract:
Abstract Objective: To explore the anti tumor effect of tumor necrosis factor related apoptosis inducing ligand (TRAIL) against giant cell tumor of bone (GCT), and to study the influence of IFN γ on the anti tumor effects of TRAIL and the possible mechanisms. MethodsFresh specimens were obtained from 9 patients who were pathologically diagnosed as having GCT in the orthopaedics department of No. 301 Hospital PLA from 2003 to 2006. The GCT cells from specimens were divided into 4 groups: control group, TRAIL group, IFN γ group and IFN γ plus TRAIL group. The cell inhibition was examined by CCK 8 assay. Cell apoptosis was detected by flow cytometric analysis and TUNEL assays. RT PCR was applied to semi quantitatively assay the mRNA expression of TRAIL, DR4 and DR5 in GCT cells before and after the treatment with IFN γ (500 U/ml). Results: The GCT cell survival rate was （98.64±0.31）% in the control group. TRAIL alone (100, 500,1 000 μg/L) had no obvious effect on tumor cell proliferation. After treatment with IFN γ at 500 and 1 000 U/ml , the tumor cell survival rates were (94.05±1.89) % and (90.47±2.66) %, respectively. After treatement with IFN γ (500 U /ml) and TRAIL (100,200 μg/L), the tumor cell survival rates were (84.65±246)% and (77.65±3.14)%, respectively; and FCM showed that their apoptosis rates were (2794±288)% and (38.65±2.46)%, respectively ; the apoptosis rate was (1.77±0.49)% in the control group. TUNEL revealed that the apoptosis rates were (1963±351)% and (29.28±4.80)% , respectively; and the rate was (1.1±0.17)% in the control group. RT PCR showed that the expression levels of TRAIL, DR4 and DR5 in tumor cells were up regulated after treatment with IFN γ (500 U /ml) for 24 h. Conclusion: GCT cells are not sensitive to TRAIL. IFN γ can up regulate the apoptosis rate of GCT cells induced by TRAIL, which might be associated with the up regulation of TRAIL, DR4 and DR5 mRNA expression by IFN γ.
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Supported by the National High Technology Research and Development Program of China （No.2002AA214081）
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