title: Sensitization and apoptosis augmentation of K562/ADM cells by anti-multidrug resistance gene peptide nucleic acid and antisense oligodeoxyribonucleotide.
abstract: OBJECTIVE
  To investigate the reversal effect and apoptosis enhancement of peptide nucleic acid (PNA) and antisense oligodeoxyribonucleotide (ASODN) targeted to multidrug resistance gene (mdr1) on human multidrug resistant leukemia K562/ADM cells.
  
  
  METHODS
  A 15-mer PNA and the same sequence of ASODN, complementary to the 5' end of the AUG initiator codon-containing region of mdr1 messenger RNA (MDR1-PNA, MDR1-ASODN), were designed and synthesized. Proliferation and sensitivity to adriamycin of K562/ADM cells treated with MDR1-PNA- and MDR1-ASODN were analyzed with a MTT colorimetric assay. Apoptotic morphologies, P-glycoprotein (P-gp) expression, intracellular adriamycin accumulation, and cell cycle were measured.
  
  
  RESULTS
  MDR1-PNA 1 to 10 micromol/L and MDR1-ASODN 2 to 20 micromol/L alone had no inhibitory effects on the proliferation of K562/ADM cells, but significantly inhibited the growth of K562/ADM cells cultured in adriamycin-containing medium. After treatment with MDR1-PNA and MDR1-ASODN, intracellular adriamycin accumulation in K562/ADM cells increased greatly and P-gp synthesis was strikingly reduced. The resistance to adriamycin of the drug-resistant cells was partly reversed and the cells were induced to apoptosis by adriamycin. The reversal efficacy of MDR1-PNA was 3.1-fold higher than that of the same sequence of MDR-ASODN, but neither MDR1-PNA nor MDR1-ASODN could completely block the mdr1/P-gp expression.
  
  
  CONCLUSIONS
  Sequence-special PNA targeted to mdr1 gene more effectively than the same sequence of MDR1-ASODN inhibited the expression of P-glycoprotein to overcome the drug-resistance.
authors.affiliation: Laboratory Center for Medical Science, Lanzhou Medical College, Lanzhou 730000, China. weihl@public.lz.gs.cn.
authors.forename: Hu-Lai
authors.initials: HL
authors.lastname: Wei
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Jing
authors.forename: De-Cheng
authors.initials: DC
authors.lastname: Bai
authors.forename: Lan-Fang
authors.initials: LF
authors.lastname: Ma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D020135:Peptide Nucleic Acids / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D020319:Oligodeoxyribonucleotides, Antisense; D020135:Peptide Nucleic Acids; D004317:Doxorubicin