Anti-K-ras ribozyme induces growth inhibition and increased chemosensitivity in human colon cancer cells

Cancer Gene Ther. 2000 Mar;7(3):495-500. doi: 10.1038/sj.cgt.7700125.

Abstract

Colon cancer is one of the carcinomas that is resistant to a variety of therapies. To develop a new therapy by regulating the activated K-ras gene in colon cancers, we prepared synthetic DNA encoding the ribozyme (catalytic RNA), and inserted it into an expression vector (LNCX) originated from a retrovirus. Transfection of the vector into SW620 human colon cancer cells brought about significant suppression of K-ras mRNA synthesis and inhibition of the cell growth. Studies in athymic mice, in which K-ras ribozyme-introduced SW620 cells were transplanted, also revealed a marked reduction of tumor growth in vivo. Furthermore, the ribozyme-introduced tumors became more sensitive to treatment with anti-cancer drugs such as cisplatin, adriamycin, 5-fluorouracil, vincristine, and etoposide. These data suggest that the possible efficacy of anti-K-ras ribozyme increases the chemosensitivity of human colon cancers as well as the inhibitory effect on the growth of human colon cancers.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Colonic Neoplasms / chemistry
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology*
  • Electroporation
  • Gene Expression Regulation, Neoplastic
  • Gene Transfer Techniques
  • Genetic Vectors / genetics
  • Growth Inhibitors / genetics*
  • Growth Inhibitors / pharmacology*
  • Humans
  • Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • RNA, Catalytic / genetics
  • RNA, Catalytic / pharmacology*
  • Retroviridae / genetics
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Growth Inhibitors
  • RNA, Catalytic
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)