抗人DR4、DR5单克隆抗体诱导神经胶质瘤细胞凋亡的实验研究

目的：探讨抗死亡受体DR4、DR5单克隆抗体（mAb）FMU1．4、FMU1．5对3株神经胶质瘤细胞株U343（敏感株）、U138（部分敏感株）、U373（耐受株）的杀伤作用及机制。方法：采用流式细胞术、RT—PCR、免疫细胞化学法、MTT比色法、电泳、DNA倍体分析和Westem blot等方法。结果：DR5在U343高表达；DR4在U373低表达。U343对FMU1．5敏感并呈剂量依赖性、对FMU1．4部分敏感；U138对FMU1．5部分敏感，对FMU1．4耐受；U373对两种抗体耐受。结论：FMU1．4、FMU1．5能不同程度地诱导三株细胞凋亡，其机制与DR4、0115、细胞色素C和FLIP的表达有关。

Anti-human DR5/DR4 monoclonal antibody induce glioma cell lines apoptosis

Objective:To study the cytotoxic effects on three glioma cell lines U343, U138, U373 induced by anti-human DR5/DR4 monoclonal antibodies(FMU1.5/FMU1.4) and the underlying mechanism.Methods:Expression of DR4/DR5 was quantitated by flow cytometry and DR/4DR5 mRNA detected by RT-PCR. Cytotoxicity exerted by FMU1.4/FMU1.5 on three cell lines was measured by MTT colorimetry and the induced apoptosis was determined by agarose gel electrophoresis, DNA ploidy analysis was studied by flow cytometry.Results:The expression of DR5 on U343 cells was higher and the expression of DR4 on U373 cells was lower. Cell line U343 was sensitive to FMU1.5 and in a dose dependent manner, but it was partially sensitive to FMU1.4; Cell line U138 was partially sensitive to FMU1.5 and resistant to FMU1.4; Cell line U373 was insensitive to two antibodies.Conclusion:Apoptosis induced by monoclonal antibodie FMU1.4/FMU1.5 vary among three cell lines. The underlying mechanism may be relevant to DR4/DR5 expression,the release of cytochrome C and FLIP.