[Enhancement of glioma cell apoptosis induced by anti-human DR5/DR4 monoclonal antibodies by sub-toxic dose of doxorubicin in human].
OBJECTIVE
To study the cytotoxic effects of doxorubicin on apoptosis in glioma cell lines U343, U138, U373 induced by anti-human DR4/DR5 monoclonal antibodies (FMU1.4/FMU1.5) and the underlying mechanism.


METHODS
Expression of DR4/DR5 was quantitated by flow cytometry. 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. The expression of cytochrome C, FLIP and Ca2+ concentration were also measured.


RESULTS
Following the treatment of doxorubicin DR4 and DR5 were highly expressed on the cell surface; The apoptosis of U138 and U373 induced by FMU1.4 and FMU1.5 was stronger. expression of cytochrome C and Ca2+ concentration were enhanced, whereas the expression of FLIP was downregulated.


CONCLUSIONS
Subtoxic doxorubicin applied with antibodies caused higher cell death rate of glioma cells, which may be relevant to DR4/DR5, the release of cytochrome C and FLIP and Ca2+ concentration.
Zhuang
Guo-hong
GH
Department of Immunology, School of Basic Medical Science, Jilin University, Changchun 130021, China. zhuangguohong@yahoo.com.cn
Song
Yu-guo
YG
Bi
Sheng-li
SL
Du
Bai-rong
BR
Zhu
Xun
X
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005910:Glioma / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D004317:Doxorubicin; D045304:Cytochromes c; D002118:Calcium