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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 19, 2013
[In vitro effect of lovastatin on NB4 promyelocytic leukemia cells]
1First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou 215006, China.
Objective:
To explore the effect of lovastatin(LOV) on cell growth, apoptosis and differentiation of NB4 cells and elucidate some of the possible mechanism.
Methods:
Cell proliferation and viability were analyzed by MTT assay and trypan blue exclusion assay, cell differentiation by NBT reduction. Cell morphological examination, DNA electrophoresis, flow cytometry, TUNEL in situ hybridization and semi-quantitative RT-PCR were performed to determine cell apoptosis. H,K,N-ras gene expression was investigated by RT-PCR and p21Ras protein expression by flow cytometry.
Results:
1. LOV inhibited the proliferation of NB4 cells with a lC50 of 12.59 mumol/L. 2. LOV induced apoptosis of NB4 cells, affected the cell cycle progression and arrested NB4 cells in G1/S phase. Bcl-2 mRNA was down-regulated by LOV in a time-dependent manner. 3. LOV could not induce the differentiation of NB4. 4. LOV did not increase the expression of H,K,N-ras mRNA, but decrease p21Ras protein expression on the cellular membrane.
Conclusion:
LOV can inhibit proliferation, induce apoptosis and interfere with cell cycle progression, but not induce differentiation of NB4. Inhibition of p21Ras protein isoprenylation is considered to be the major mechanism of LOV affecting NB4 cells.
