死亡结构域沉默子参与两型TNF-α胞毒效应机制的研究

Studies of the role of SODD in the cytotoxicity mediated by the two forms of TNF-α

目的 比较两型TNF对肿瘤细胞的胞毒效应与SODD表达关系的异同。方法 应用MTT法检测两型TNF对HL6 0和U937的杀瘤效应。应用RT PCR技术 ,检测HL6 0和U937肿瘤细胞株SODD、TNFR1的表达情况及两型TNF对其影响。结果 对S TNF耐受而对TM TNF敏感的HL6 0细胞内接头分子SODD表达水平明显高于TNFRI表达水平 ,而对两型TNF均敏感的U937细胞内SODD表达相对极低于TNFRI的表达 ;S TNF对两种细胞内SODD的表达无影响 ,而TM TNF可下调胞内SODD表达水平。结论 肿瘤细胞内SODD的表达水平与TNF的杀伤效应呈负相关 ,TM TNF可下调SODD的表达从而比不能下调SODD表达的S TNF有更广的杀瘤谱 ,对SODD表达的影响不同可能是两型TNF杀瘤效应存在差异的原因之一。

Objective To study the correlation between the silencer of death domain (SODD) expression and the cytotoxicity mediated by transmembrane TNF-α (TM-TNF-α) and by secreted TNF-α (S-TNF-α). Methods The cytotoxicity of S-TNF-α and TM-TNF-α to the two kinds of tumor cell lines HL60 and U937 was explored and compared by MTT assay. The expressions of SODD and TNFR1 in cells and the effects of S-TNF-α and TM-TNF-α on the expressions were examined by RT-PCR. Results The expression of SODD was higher than that of TNFR1 in HL60 cell, which was susceptive to TM-TNF-α but not to S-TNF-α. But the expression of SODD was lower than that of TNFR1 in U937 cell, which susceptive to both forms of TNF-α. S-TNF-α had no effect on the expression of SODD in HL60 and U937 cells, while TM-TNF-α was able to down-regulate the expression of SODD in HL60 and U937 cells. Conclusion The results suggest that the expression of SODD in tumor cells is negatively correlated with the cytotoxity of TNF-α. TM-TNF-α, which could down-regulate the SODD expression, has a broader tumorcidal spectrum than S-TNF-α, which could not down-regulate the SODD expression. This may be one of the reasons why TM-TNF-α and S-TNF-α have different antitumor effects.