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.