[Study of molecular mechanism of doxorubicin enhancement of TRAIL, inducing apoptosis of myeloma cell line KM3].
OBJECTIVE
To investigate the molecular mechanism of doxorubicin enhancement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inducing apoptotic effect on multiple myeloma cell line KM3.


METHODS
Apoptosis was studied independently through flow cytometry analysis and TUNEL staining. The expression of death receptor 5 (DR5) and nuclear factor P65 in nuclear was examined by Western blot.


RESULTS
The apoptosis ratio of KM3 cells was 20.88%, 40.03%, 57.87%, 60.82% respectively when treated with different concentration of TRAIL (10, 20, 50, 100 ng/ml) combining with doxorubicin. It is markedly higher than the group treated with TRAIL or doxorubicin alone. DR5 expression increased while P65 decreased as the doses of doxorubicin increased when KM3 cells treated with doxorubicin (0.5, 1.0, 2.0 and 4.0 microg/ml) plus 20 ng/ml TRAIL.


CONCLUSIONS
Increasing the expression of DR5 and nuclear transferring of P65 are the important molecular mechanism by which doxorubicin enhances TRAIL-inducing apoptosis of KM3 cells.
Wang
Hua-fang
HF
Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Chen
Zhao-hui
ZH
Sun
Chun-yan
CY
Hu
Yu
Y
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D051996:Transcription Factor RelA; D004317:Doxorubicin