[Study on proliferation inhibiting and apoptosis inducing effects of cerulenin on multiple myeloma cells].
OBJECTIVE
To determine whether fatty acid synthase (FAS) is expressed in human multiple myeloma( MM) cells and investigate the proliferation inhibition effect of fatty acid synthase inhibitor cerulenin on multiple myeloma cell line U266 and its mechanism.


METHODS
FAS mRNA expression in human MM cell line U266, RPMI8226 cell was assayed by RT-PCR. The proliferation inhibition rate of U266 cells was assayed by MTr analysis. Cell apoptosis and cycle distribution were evaluated by flow cytometry (FCM).


RESULTS
FAS mRNA was highly expressed in human multiple myeloma cell lines as compared with healthy donor PBMNCs. After U266 cells were treated with cerulenin (the concentrations from 5 microg/ml to 640 microg/ ml) for 24 h, the cell proliferation was markedly inhibited with a dose related manner, while the inhibition rate of human skin fibroblast cells were all lower than 30%. When U266 cells were treated with 20 pjg/ml cerulenin for 12 h and 24 h, the early apoptosis rate revealed by Annexin V/PI were 56. 9% and 69. 3% respectively, being higher than that of the blank controls (4. 3% and 1.8%, P < 0. 01). Cell cycle analysis showed it was blocked in S phase. Conclusion FAS is highly expressed in human MM. Cerulenin could induce apoptosis and inhibit proliferation of U266 cells. FAS might be a new potential target for multiple myeloma treatment.
Wang
Wei-qin
WQ
The Second Affiliated Hospital of Medical School, Zhejiang University, Hangzhou 310009, China.
Zhao
Xiao-ying
XY
Xu
Geng-bo
GB
Liang
Yun
Y
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002569:Cerulenin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D002569:Cerulenin; D064429:Fatty Acid Synthases