Simvastatin selectively inhibits proliferation and induces apoptosis of chronic myelogenous leukemia cells / 北京大学学报(医学版)

ABSTRACT

Objective: To explore the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (the rate-limiting enzyme of cholesterol synthesis) on the proliferation and apoptosis of chronic myelogenous leukemia (CML) cells. Methods: Both normal and CML bone marrow progenitor cells were assayed in semisolid methylcellulose culture after incubation for 24 hours in suspension culture with 10 mg*L－1 simvastatin. Also, sub-G1 cells and DNA end-labeling positive cells as apoptotic cells were identified by flow cytometry after being exposed to simvastatin for 72 hours. Results: Simvastatin selectively inhibited proliferation and induced apoptosis of CML cells, but had no much influence on normal bone marrow cells. Conclusion: CML cells are more sensitive to a short-term exposure to simvastatin than normal bone marrow cells. It will be a promisingly effective chemotherapeutic agent or in vitro purging agent in autologous stem cell transplantation for the treatment of CML.