B. Scaggiante et al., EFFECT OF UNMODIFIED TRIPLE HELIX-FORMING OLIGODEOXYRIBONUCLEOTIDE TARGETED TO HUMAN MULTIDRUG-RESISTANCE GENE MDR1 IN MDR CANCER-CELLS, FEBS letters, 352(3), 1994, pp. 380-384
The human mdr1 gene encodes a transmembrane glycoprotein the over-expr
ession of which is associated with development of multidrug resistance
in human tumor cells. A negative modulation of human mdr1 has been at
tempted via a 27-mer unmodified triple helix-forming oligonucleotide,
named 1D, targeted to a homopurine sequence in the coding region of th
e gene. By administering 10 mu M of 1D we could find a significant red
uction in MDR1 mRNA levels in the human drug-resistant cell line CEM-V
LB100. This effect appears to be specific and due to a transient block
of RNA polymerase mediated by triple helix formation.