In vivo evaluation of intravesical paclitaxel and combined bcl-xL antisense oligodeoxynucleotide treatment for orthotopic urothelial carcinoma

J Cancer Res Clin Oncol. 2009 May;135(5):679-86. doi: 10.1007/s00432-008-0500-5. Epub 2008 Oct 22.

Abstract

Purpose: To evaluate intravesical paclitaxel monotherapy and combined treatment with antiapoptotic bcl-xL antisense oligodeoxynucleotides (AS-ODNs) on urothelial carcinoma (UC).

Methods: Forty-eight FoxN(rnu) athymic nude rats with orthotopic human bladder UC were randomized to four treatment groups [1, paclitaxel; 2, paclitaxel/bcl-xL AS-ODNs; 3, bcl-xL AS-ODNs (control); 4, medium (control)]. Three consecutive instillations were applied and weekly endoscopic tumor size measurements were performed.

Results: Significant tumor size reduction was achieved in groups 1 and 2 (each P < 0.0001), whereas continuous UC growth was observed in control animals (groups 3 and 4; P < 0.0001 and P < 0.0020). Complete tumor eradication was achieved in four treated animals (groups 1 and 2). No significant difference in chemoresection effects was found between groups 1 and 2 (P = 0.2251).

Conclusions: We present an in vivo evaluation of intravesical treatment with paclitaxel and combined bcl-xL AS-ODNs. Despite efficient tumor size reduction, no gain was observed when adding bcl-xL AS-ODNs in this experimental setting.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravesical
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Combined Modality Therapy
  • Disease Models, Animal
  • Humans
  • Kidney / pathology
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / therapeutic use*
  • Paclitaxel / administration & dosage
  • Paclitaxel / therapeutic use*
  • Rats
  • Rats, Nude
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Urologic Neoplasms / drug therapy*
  • Urologic Neoplasms / genetics
  • Urologic Neoplasms / pathology
  • bcl-X Protein / genetics*

Substances

  • Antineoplastic Agents, Phytogenic
  • Bcl2l1 protein, rat
  • Oligonucleotides, Antisense
  • bcl-X Protein
  • Paclitaxel