Figure 4.
LDL accumulation is differentially affected in AML cell lines by nontoxic treatments with mevastatin, DNR, and ARA-C, and DNR plus statin treatments can be used to uncover the ability of AML cells to mount LDL increments when new cholesterol synthesis is blocked. LDL accumulation was measured in untreated NB4, KG1a, and HL60 AML cells, and in the same cells after various drug treatments, as described more completely in “Materials and methods.” Wilcoxon rank sum tests were used to compare means of treated and untreated AML samples, with 2-tailed tests of significance. LDL accumulation was significantly increased by 6.25 μM mevastatin (MEV) treatments in NB4 (P = .0001) and KG1a (P = .02) cells. LDL accumulation was significantly increased by DNR (P = .001) but not ARA-C (P = .27) in NB4 cells. LDL accumulation was not increased by DNR or ARA-C in KG1a cells, but DNR plus mevastatin (+D+M) cotreatments produced LDL accumulation increments that were supra-additive (P = .05 with DNR only, P = .06 with MEV only) compared to increments measured in KG1a cells treated with statin or DNR alone. HL60 cells did not show increased LDL accumulation after mevastatin, DNR, or ARA-C treatments, and combination treatments did not produce supra-additive increments. Mean LDL accumulation increments are plotted, and error bars represent SEM. Bold horizontal lines indicate mean.