title: [Arsenic trioxide inhibits P-glycoprotein expression in multidrug-resistant human leukemia K562/ADM cell line that overexpresses mdr-1 gene and enhances their chemotherapeutic sensitivity].
abstract: OBJECTIVE
  To investigate the effects of arsenic trioxide (As(2)O(3)) on the apoptosis and P-glyco-protein (P-gp) expression of multidrug-resistant human leukemia K562/ADM cells, and the combined effects of As(2)O(3) with conventional chemotherapeutic agents.
  
  
  METHODS
  Multidrug-resistant human leukemia cell line K562/ADM that overexpresses mdr-1 gene was used as the target cells. The cell proliferating activity was assessed with a MTT assay. Cell morphology was examined by light microscopy, confocal microscopy and electron-microscopy. P-gp expression, cell-cycle status were determined by flow cytometry.
  
  
  RESULTS
  K562/ADM cells were highly resistant to adriamycin, and cross-resistant to daunorubicin and etoposide. As(2)O(3) at concentrations of 0.5 to 20 micromol/L inhibited the proliferation of K562/ADM cells, and K562/ADM cells were more sensitive to As(2)O(3) than their parent K562 cells did. As(2)O(3) induced marked apoptosis of K562/ADM cells showed by typical apoptotic morphological changes and the appearance of high sub-G(1) cell population. As(2)O(3) significantly inhibited the P-gp expression in K562/ADM cells, and exerted a synergistic effect on the enhancement of the cell sensitivity to adriamycin, daunorubicin and etoposide.
  
  
  CONCLUSIONS
  As(2)O(3) induces growth-inhibition and apoptosis of multidrug-resistant K562/ADM cells, and augments synergistically the sensitivity of the cells to conventional chemotherapeutic agents via down-regulation of P-gp expression.
authors.affiliation: Laboratory Center for Medical Science, Lanzhou Medical College, Lanzhou 730000, China.
authors.forename: Hu-lai
authors.initials: HL
authors.lastname: Wei
authors.forename: Xiao-jian
authors.initials: XJ
authors.lastname: Yao
authors.forename: Yu-ning
authors.initials: YN
authors.lastname: Li
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: Huai-shun
authors.initials: HS
authors.lastname: Zhao
authors.forename: De-cheng
authors.initials: DC
authors.lastname: Bai
authors.forename: Xiao
authors.initials: X
authors.lastname: Peng
authors.forename: Lan-fang
authors.initials: LF
authors.lastname: Ma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D010087:Oxides / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D005047:Etoposide; D004317:Doxorubicin; D000077237:Arsenic Trioxide; D003630:Daunorubicin