[Inhibition of multidrug resistance related P-gp expression in human neuroblastoma by antisense peptide nucleic acid]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005 Jun;27(3):300-4.
[Article in Chinese]

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Animals
  • Drug Resistance, Multiple / genetics*
  • Humans
  • Nervous System Neoplasms / metabolism*
  • Neuroblastoma / metabolism*
  • Oligonucleotides, Antisense / pharmacology
  • Peptide Nucleic Acids / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transfection
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Oligonucleotides, Antisense
  • Peptide Nucleic Acids
  • RNA, Messenger