title: [Effect of RAD001 or plus LBH589 on the proliferation, apoptosis and drug resistance in chemoresistant acute myeloid leukemic cells].
abstract: OBJECTIVE
  To investigate the effects of everolimus (RAD001) or plus panobinostat (LBH589) on the proliferation, apoptosis and drug resistance in chemoresistant acute myeloid leukemic cells.
  
  
  METHODS
  HL-60/ADM cells were treated with RAD001 alone or with LBH589. Proliferation and apoptosis were evaluated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, Hoechst33342 and AnnexinV-FITC/PI stain. The altered expressions of multidrug resistance-associated protein 1 (MRP1) and intercellular adriamycin accumulation were analyzed by flow cytometry. The change in protein level was analyzed by Western blot.
  
  
  RESULTS
  Effective proliferative inhibition and apoptotic induction in HL60/ADM cells were observed in the treatment of 10 - 50 µmol/L RAD001. The maximal effect was shown for the concentration of 30 µmol/L RAD001 at 48 and 72 hours. The inhibition ratio remained unchanged with the adjustment of drug doses (P < 0.05). Moreover, there was no synergistic effects in the treatment with different concentration of RAD001 and LBH589 (CI ≥ 1.0). A down-regulation of MRP1 (93.9% ± 4.2% vs 79.10 ± 3.28%) and an up-regulation of adriamycin (8.53 ± 0.68% vs 15.37% ± 1.46%) were induced by the treatment with 10 µmol/L RAD001 (both P < 0.01). RAD001 inhibited the p53-dependent expression of MRP1 via an inhibition of phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway.
  
  
  CONCLUSIONS
  The combined treatment of RAD001 and LBH589 has no synergistically inhibitory effect on HL60/ADM cells. But the sole treatment of RAD001 may inhibit proliferation, induce apoptosis and accumulate intercellular adriamycin through a down-regulated expression of MRP1 in HL60/ADM cells via an inhibition of PI3K/Akt/mTOR signaling pathway.
authors.affiliation: Department of Hematology, Southern Medical University, Guangzhou, China.
authors.forename: Xue-jie
authors.initials: XJ
authors.lastname: Jiang
authors.forename: Fan-yi
authors.initials: FY
authors.lastname: Meng
authors.forename: Kai-kai
authors.initials: KK
authors.lastname: Huang
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D000068338:Everolimus; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles; D000077767:Panobinostat; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat; D000068338:Everolimus; D020123:Sirolimus