Chemosensitization of bladder cancer cells by survivin-directed antisense oligodeoxynucleotides and siRNA

Cancer Lett. 2006 Feb 8;232(2):243-54. doi: 10.1016/j.canlet.2005.02.027.

Abstract

Survivin is known to be overexpressed in numerous tumor types including human bladder cancer and to cause resistance to radiation and chemotherapy. Therefore, we tested the antisense oligodeoxynucleotide AS-SVV286 and the small interfering RNA si-SVV284 to down-regulate survivin in the BCa cell lines EJ28 and 5637 thereby acting as sensitizers for chemotherapy. Pretreatment with these inhibitors followed by chemotherapy caused an enhanced decrease in cell viability. The observed reduction in cell counts associated with increased rates of apoptosis paralleled the degree of reduction of survivin expression that was achieved more efficiently by the siRNA than by the AS-ODN. Nevertheless, both therapy approaches in combination with all tested chemotherapeutics provoked a remarkable inhibition of viability and may serve as suitable additive tools for chemosensitization of bladder cancer cells.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / antagonists & inhibitors*
  • Microtubule-Associated Proteins / genetics
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Oligodeoxyribonucleotides, Antisense / pharmacology*
  • RNA, Small Interfering / pharmacology*
  • Survivin
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Small Interfering
  • Survivin