| Objective : To investigate the difference of lipid metabolic characteristic between leukemiacells and normal cells and to explore an effective target way of inhibiting the proliferation of leukemic cells .Methods: Endogenous cholesterol synthetic pathway was inhibited by low dose atorvastatinand offered the cells with exogenous low density lipoprotein (LDL) according to the method which is found by Fanqing Meng but modified by us. Methabenzthiazuron (MTT) assay was used to detect cells growth inhibiting rate and therefore the activity of LDL receptor was judged by it. Ultraviolet spectrophotometry was used to measure the 3-hydroxy-3-methylglu-taryl-coenzyme A (HMG-CoA) reductase activity. After above-mentioned cells were treated with atorvastatin in different doses and different time, MTT assay was used to measure the cellular proliferation. Cells in logarithmic growth phase were adjusted to 100μl each well in 96 wells cell culture flasks . Atorvastatin dissolved in RPMI 1640 medium containing 10% FCS was adjusted to 10,20,40,80 and 160μmol / L and 100μl each well respectively. The well which filled with 100μl of RPMI 1640 medium containing 10% FCS instead of atorvastatin and 100μl of above cells cultivation systems served as normal control.Results : The LDL receptor and HMG-CoA reductase activities were elevated in K562 andHL-60 cells compared with HK-2 cells (p<0.05). Atorvastatin inhibited the proliferation of K562 andHL-60 cells in a dose- and time-dependent way ,that is to say ,cells survival rate decreased as the doses of Atorvastatin increased. Atorvastatin inhibited the proliferation of HK-2 cells while it was not related with different dose and time.Conclusions :The activities of LDL receptor and HMG-CoA reductase are elevated inleukemia K562 and HL-60 cells. Atorvastatin inhibits proliferation of K562 and HL-60 cells. MTT assay is reliable ,easy and safe in measuring the activity of LDL receptor. Objective : To explore variation and its significance of LDL receptor and HMG-CoA reductase activity in bone marrow cells of patients with acute leukemia .Methods: The LDL receptor and HMG-CoA reductase activities were analysed in 20 cases of nonmalignant hematologic disease and 56 cases of acute leukemia (including initial treatment group, complete remission group, relapse group, continuous complete remission group and non-remission group ) in the same way described in Part One .The effect of atorvastatin on the proliferation of acute leukemic cells was also assayed in vitro by the same method described in Part One.Results : The LDL receptor and HMG-CoA reductase activities were elevated in initial treatment group , relapse group and non-remission group compared with nonmalignant hematologic disease group (p <0.001).There were no statistical significance among complete remission group, continuous complete remission group and nonmalignant hematologic disease group (p >0.05). The proliferation of cells in initial treatment group , relapse group and non-remission group was inhibited by atorvastatin in a dose- and time-dependent way .The proliferation of cells in complete remission group, continuous complete remission group and nonmalignant hematologic disease group was also inhibited by atorvastatin while it was not related with dose and time.Conclusions :The activities of LDL receptor and HMG-CoA reductase were obviously elevated in initial leukemia patients compared with nonmalignant hematologic disease group.Both of them decreased to the level as much as nonmalignant hematologic disease group when the patient is in CR but increased again when replased and in non-remission.The activities of LDL receptor and HMG-CoA reductase play an role in the diagnosis, predicting replase and assessing prognosis of acute leukemia. Atorvastatin inhibited proliferation of cells of patients with acute leukemia. It is possible for HMG-CoA reductase inhibitor to serve as adjunctive therapy for leukemia. It is reasonable for a target therapy with the drugs carried by LDL. |
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