Telomerase inhibition by synthetic nucleic acids and chemosensitization in human bladder cancer cell lines

Methods Mol Biol. 2007:405:9-22. doi: 10.1007/978-1-60327-070-0_2.

Abstract

The knockdown of genes that are over-expressed in cancer, and function in tumor onset and/or progression, is an attractive tool to impair the growth of tumor cells. Synthetic nucleic acids such as antisense oligodeoxynucleotides (AS-ODNs) or small-interfering RNAs (siRNAs) were applied against different tumor-associated transcripts, including the human telomerase reverse transcriptase (hTERT), to inhibit the proliferation of tumor cells and to sensitize them against chemotherapeutic (CT) agents. The efficacy of nucleic acid-based inhibitors was evaluated in vitro by determining the extent of down-regulation of the respective target mRNA and protein expression as well as by extensively investigating growth properties (e.g., viability, proliferation, apoptosis, and cell-cycle distribution) of the affected tumor cells. Methods for a successful down-regulation of hTERT and for the quantitative determination of resulting effects on cellular growth were described herein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Count
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation / drug effects*
  • Drug Screening Assays, Antitumor
  • Enzyme Repression / drug effects
  • Fluorescence
  • Humans
  • Molecular Biology / methods*
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology*
  • Telomerase / antagonists & inhibitors
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Transfection
  • Tumor Stem Cell Assay
  • Urinary Bladder Neoplasms / enzymology*
  • Urinary Bladder Neoplasms / genetics*

Substances

  • Oligonucleotides, Antisense
  • RNA, Small Interfering
  • TERT protein, human
  • Telomerase