title: AZT and emodin exhibit synergistic growth-inhibitory effects on K562/ADM cells by inducing S phase cell cycle arrest and suppressing MDR1 mRNA/p-gp protein expression.
abstract: BACKGROUND
  Previous studies have demonstrated that both 3'-azido-3'-deoxythymidine (AZT) and emodin, a traditional chemotherapy agent, can inhibit the growth of many types of cancer cells.
  
  
  OBJECTIVE
  This study aimed to evaluate the effect of AZT and emodin on adriamycin-resistant human chronic myelogenous leukemia (K562/ADM) cells, determine the expression of multidrug resistance 1 (MDR1) mRNA/p-glycoprotein (p-gp) protein, a protein known to induce resistance to anticancer agents, and to elucidate the underlying molecular mechanisms.
  
  
  METHODS
  K562/ADM cells were treated with AZT (10-160 μM) or emodin (5-80 μM) for 24, 48 and 72 h and cell viability was measured using the MTT assay. The effect of AZT (16.5, 33 and 66 μM) and emodin (6.1, 17.6 and 33.2 μM) on K562/ADM cell cycle distribution was determined by flow cytometry, and MDR1 mRNA/p-gp protein expression was determined by real time RT-PCR and western blotting.
  
  
  RESULTS
  The growth suppression of emodin was dramatically enhanced by AZT in K562/ADM cells. The IC50 of AZT and emodin was lower than that of emodin alone. All examined combinations of AZT and emodin yielded a synergetic effect (CI < 1). Furthermore, AZT and emodin altered the cell cycle distribution and led to an accumulation of cells in S phase. Meanwhile, the expression of MDR1 mRNA/p-gp protein was markedly decreased.
  
  
  CONCLUSIONS
  These results show a synergistic growth-inhibitory effect of AZT and emodin in K562/ADM cells, which is achieved through S phase arrest. MDR1 might ultimately be responsible for these phenomena.
authors.affiliation: School of Life Science, Lanzhou University , Lanzhou , China .
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Liu
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Sun
authors.forename: Che
authors.initials: C
authors.lastname: Chen
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Qi
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D004642:Emodin / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D012333:RNA, Messenger / Q000235:genetics; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D015215:Zidovudine; D004317:Doxorubicin; D004642:Emodin