Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR

Oncogene. 2005 Sep 29;24(43):6492-501. doi: 10.1038/sj.onc.1208731.

Abstract

Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70-80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Drug Screening Assays, Antitumor / methods
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Liposomes / administration & dosage*
  • Liposomes / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • RNA, Antisense / genetics
  • RNA, Antisense / pharmacology*
  • Telomerase / antagonists & inhibitors*
  • Telomerase / genetics
  • Telomerase / metabolism
  • Tumor Cells, Cultured

Substances

  • Enzyme Inhibitors
  • Liposomes
  • RNA, Antisense
  • Telomerase