Inhibition of tumor angiogenesis during cisplatin chemotherapy for bladder cancer improves treatment outcome

Urology. 2005 Feb;65(2):395-9. doi: 10.1016/j.urology.2004.09.041.


Objectives: To investigate the effect of inhibiting tumor angiogenesis during cisplatinum-(II)-diamine dichloride (cisplatin) chemotherapy of bladder cancer (BC) in a rat model.

Methods: Bladder cancer was induced in 64 male rats using 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine in their water supply for 20 weeks. The animals were then divided randomly into four groups of 16 rats each: a control BC group (group 1); a BC group treated with cisplatin (0.25 mg/kg body weight) by intraperitoneal injection twice every week (group 2); a BC group treated with the antiangiogenic factor TNP-470 (30 mg/kg body weight) by intraperitoneal injection twice every week (group 3); and a BC group treated with cisplatin plus TNP-470 (group 4, treatment regimens as described). Per group, 4 rats were killed weekly after the start of treatment, for 4 weeks. BC was confirmed using histologic characteristics, and the treatment outcomes were determined by measuring tumor microvascular density and cell proliferation and apoptosis indexes (PI and AI, respectively).

Results: All animals had confirmed BC. Both group 3 (TNP-470) and group 4 (cisplatin plus TNP-470) had significantly decreased microvascular density compared with group 1 (P <0.05). Although both the PI and AI were significantly different between group 4 (cisplatin plus TNP-470) and group 1 (control BC; P <0.05), neither the PI nor AI was significantly different between group 2 (cisplatin) and group 4 (cisplatin plus TNP-470; P >0.05).

Conclusions: TNP-470 in conjunction with cisplatin chemotherapy resulted in a decrease in the microvascular density of BC in a rat model. However, TNP-470 did not appear to have a significant impact on the cisplatin effect against BC as measured by apoptosis and cell proliferation.

Publication types

  • Comparative Study

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis
  • Carcinoma, Transitional Cell / blood supply
  • Carcinoma, Transitional Cell / chemically induced
  • Carcinoma, Transitional Cell / drug therapy*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cyclohexanes
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Injections, Intraperitoneal
  • Male
  • Neovascularization, Pathologic / drug therapy*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Random Allocation
  • Rats
  • Sesquiterpenes / administration & dosage
  • Urinary Bladder Neoplasms / blood supply
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / drug therapy*


  • Angiogenesis Inhibitors
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Cyclohexanes
  • Sesquiterpenes
  • Cisplatin
  • O-(Chloroacetylcarbamoyl)fumagillol