A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth

Nat Med. 1995 Jun;1(6):528-33. doi: 10.1038/nm0695-528.

Abstract

Expression of the RI alpha subunit of cAMP-dependent protein kinase type I is enhanced in human cancer cell lines, in primary tumours, in cells after transformation and in cells upon stimulation of growth. We have investigated the effect of sequence-specific inhibition of RI alpha gene expression on in vivo tumour growth. We report that single injection RI alpha antisense treatment results in a reduction in RI alpha expression and inhibition of tumour growth. Tumour cells behaved like untransformed cells by making less protein kinase type I. The RI alpha antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to halt neoplastic growth in vivo.

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma / pathology
  • Carcinoma / therapy*
  • Cell Transformation, Viral
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Drug Screening Assays, Antitumor
  • Genetic Therapy*
  • Humans
  • Injections, Subcutaneous
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / genetics
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplasm Transplantation
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / pharmacology
  • Oligonucleotides, Antisense / therapeutic use*

Substances

  • Isoenzymes
  • Neoplasm Proteins
  • Oligonucleotides, Antisense
  • Cyclic AMP-Dependent Protein Kinases