title: [Inhibition of multidrug resistance related P-gp expression in human neuroblastoma by antisense peptide nucleic acid].
abstract: OBJECTIVE
  To investigate the efficiency of a peptide nucleic acid (PNA) delivery system by using liposome via PNA-DNA hybrids and to test the inhibitive action of antisense PNA on expression of multidrug resistance (MDR) related P-glycoprotein (P-gp) in human neuroblastoma cell line SK-N-SH.
  
  
  METHODS
  Two antisense PNAs were designed targeting at MDR-1 mRNA and then combined with partially complement DNAs respectively. The hybrids were delivered into cells using cationic liposome. The transfection efficiency, expression of P-gp and MDR-1 mRNA, intracellular adarimycin (ADM) were measured by flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and high performance liquid chromatography (HPLC).
  
  
  RESULTS
  Transfection of PNA increased the cell average fluorescence intensity significantly and the extent of increase was dependent on the concentration of PNA. After being transfected by both PNAs, P-gp expression of SK-N-SH cells decreased significantly and the intracellular ADM level was increased by about 3 times. The level of MDR-1 mRNA expression slightly decreased after transfection, but no statistical significance was observed.
  
  
  CONCLUSIONS
  PNA can be delivered into tumor cells in form of PNA-DNA hybrids by cationic liposome. Properly designed antisense PNA can inhibit MDR related P-gp expression of SK-N-SH cells efficiently and specifically.
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital, Shandong University, Jinan 250033, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.forename: Qing-lin
authors.initials: QL
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Cheng-wei
authors.initials: CW
authors.lastname: Wang
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Kong
authors.forename: Fu-sheng
authors.initials: FS
authors.lastname: Liu
authors.forename: Dao-xin
authors.initials: DX
authors.lastname: Ma
authors.forename: Ji-feng
authors.initials: JF
authors.lastname: Bian
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D009423:Nervous System Neoplasms / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020135:Peptide Nucleic Acids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; D012333:RNA, Messenger