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Cyclooxygenase-2: potential role in regulation of drug efflux and multidrug resistance phenotype

A Sorokin1

  • 1Department of Medicine, Division of Nephrology and Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. sorokin@mcw.edu

Current Pharmaceutical Design
|February 18, 2004
PubMed

Insights

Cyclooxygenase-2 (Cox-2) may enhance multidrug resistance (MDR) in cancer by increasing MDR1 transporter expression. Cox-2 inhibitors could potentially overcome this resistance, improving chemotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Multidrug resistance (MDR) in cancer chemotherapy is often linked to ATP-binding cassette (ABC) transporters, like MDR1 (P-glycoprotein).
  • Cyclooxygenase-2 (Cox-2) is constitutively expressed in many cancer cells and its role in tumor growth is debated.
  • A potential link between Cox-2 and the development of MDR phenotype needs further investigation.

Purpose of the Study:

  • To explore the relationship between Cox-2 expression and the development of multidrug resistance in cancer cells.
  • To investigate if Cox-2 activity influences the expression and function of the MDR1 transporter.
  • To assess the potential of Cox-2 inhibitors in overcoming MDR.

Main Methods:

  • Enforced expression of Cox-2 in cancer cells.
  • Assessing MDR1 expression levels.
  • Evaluating MDR1 functional activity.
  • Utilizing Cox-2 inhibitors.

Main Results:

  • Enforced expression of Cox-2 led to increased MDR1 expression.
  • Cox-2 overexpression also enhanced the functional activity of MDR1.
  • These findings suggest a causal link between Cox-2 activity and MDR1 expression.

Conclusions:

  • Cox-2 plays a role in promoting the multidrug resistance phenotype in cancer cells.
  • Targeting Cox-2 with inhibitors may reduce MDR1 function.
  • This approach could enhance chemotherapy drug accumulation and overcome tumor resistance.

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