Effects of lovastatin on ras expression and p21~(Ras) membrane localization in human promyelocytic leukemia NB4 cells in vitro / 中国病理生理杂志

ABSTRACT

AIM: To explore the effects of cholestoral and mevalonate synthesis inhibitor lovastatin (LOV) on the proliferation of NB4 cells and elucidate the mechanisms. METHODS: Cell proliferation was analyzed by MTT assay;the expression of H, K, N- ras oncogenes in NB4 cells at different time point after LOV treatment were determined by semi-quantitative RT-PCR. Both total p21 Ras protein and p21 Ras protein on the cellular membrane were examined by flow cytometry. RESULTS:①LOV inhibited the proliferation of NB4 cells. ②All three kinds of ras were expressed in NB4 cells. ③LOV caused no increase in H, K, N- ras mRNA level. Amount of total p21 Ras protein did not change as the time varied. Concomitantly,p21 Ras protein localized on the cellular membrane decreased. CONCLUSION:LOV inhibits the proliferation of NB4 cells. Targeting HMG-CoA reductase, LOV blocks the isoprenylation of p21 Ras protein which affects its anchorage on the cellular membrane. No change in the H, K, N- ras mRNA and total p21 Ras protein expression is detected.