[Inhibition of proliferation and induction of apoptosis by simvastatin in K562 leukemic cell line].
OBJECTIVE
To investigate the anti-apoptotic mechanism and explore approach to inhibiting proliferation and inducing apoptosis of chronic myclogenous leukemia (CML) cells.


METHODS
K562 cell line was used to evaluate the effects of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and the combination of simvastatin with chemotherapeutic agents on the proliferation and apoptosis of CML cells.


RESULTS
Simvastatin could significantly inhibit proliferation and induce apoptosis of K562 cells, and could increase the sensitivity of K562 cells to chemotherapeutic agents. Addition of mevalonate, the immediate product of HMG-CoA, could completely reverse this effect.


CONCLUSIONS
Simvastatin inhibited proliferation and induced apoptosis of K562 cells through inhibiting the metabolic pathway of mevalonate. It is promising that HMG-CoA reductase inhibitors may be an effective chemotherapeutic approach to the treatment of CML.
Ren
H
H
Institute of Hematology & People's Hospital, Peking University, Beijing 100044, China.
Zhang
N
N
Xu
H
H
Lu
D
D
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D019821:Simvastatin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019821:Simvastatin; D006904:Hydroxymethylglutaryl-CoA Synthase