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Cytostatic sensitivity and MDR in bladder carcinoma cells: implications for tumor therapy

H Schuldes1, J H Dolderer, C Schoch

  • 1Klinik für Urologie und Kinderurologie, St. Katharinenhospital Frechen, Germany.

International Journal of Clinical Pharmacology and Therapeutics
|April 28, 2000
PubMed

Insights

Chemotherapy resistance in bladder cancer may be overcome. R-verapamil and linolenic acid enhanced chemotherapy effectiveness by altering cancer cell membrane fluidity, improving treatment outcomes.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Chemotherapy for advanced bladder carcinoma shows suboptimal clinical success.
  • Mechanisms of chemotherapy resistance, including P-170 glycoprotein expression, are not fully understood.
  • Developing strategies to overcome drug resistance is crucial for improving bladder cancer treatment.

Purpose of the Study:

  • To investigate the potential of R-verapamil and cell membrane perturbing agents to modulate chemotherapy sensitivity in bladder cancer cells.
  • To examine the relationship between cell membrane order and drug sensitivity.
  • To identify novel agents that can enhance the efficacy of existing chemotherapeutic drugs.

Main Methods:

  • In vitro study using cisplatin-sensitive and cisplatin-resistant bladder carcinoma cell lines.
  • Assessment of cell growth rates under various treatment conditions.
  • Measurement of cell membrane order using electron-paramagnetic resonance (EPR) spectrometry.
  • Evaluation of cytotoxicity of chemotherapeutic agents alone and in combination with modulators.

Main Results:

  • R-verapamil increased doxorubicin's toxicity in cisplatin-resistant cells with high membrane order.
  • Linolenic acid demonstrated similar effects, enhancing sensitivity to doxorubicin, cisplatin, and methotrexate.
  • Bile salts (TCDC, TUDC) showed minimal impact on cytotoxicity.
  • Changes in membrane fluidity correlated with altered drug sensitivity.

Conclusions:

  • R-verapamil and linolenic acid show potential as sensitivity modulators for bladder carcinoma chemotherapy.
  • These agents may exert their effects by altering cancer cell membrane fluidity.
  • Further research into membrane-targeting agents could lead to improved bladder cancer treatment strategies.

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