Positive correlation between cyclooxygenase-2 and ABC-transporter expression in non-Hodgkin's lymphomas

Oncol Rep. 2009 Dec;22(6):1315-23. doi: 10.3892/or_00000570.

Abstract

One of the leading causes of chemotherapy failure in non-Hodgkin's lymphomas (NHLs) is multidrug resistance (MDR). MDR can be associated with expression of members of the family of ABC-transporters. Since a correlation between expression of cyclooxygenase-2 (COX-2) and MDR in various cancer cells was described, the expression of COX-2 and the ABC-transporters MDR1/P-glycoprotein (P-gp), MRP1, MRP2 and BCRP was examined in 56 previously non-treated patients by immunohistochemistry. The data show that: i) P-gp is not expressed in non-treated NHLs; ii) MRP2 can be localized in the nuclear membranes of NHL cells; iii) expression of MRP2 in the cytoplasm membrane correlates with clinical response; iv) elevated expression of BCRP is typical for the patients, who did not respond to primary chemotherapy and for cases with shorter progression-free survival time in a 30 months follow-up; and v) there is a strong correlation between COX-2 and MRP1, MRP2 and BCRP. It can be concluded that: i) BCRP may be a crucial factor involved in primary resistance of NHLs, thus it may be useful for prediction of chemotherapeutic treatment and risk of relapse; and ii) since there is strong correlation between COX-2 expression and MDR in NHLs, the application of COX-2 inhibitors may be considered for chemosensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis*
  • Aged
  • Antineoplastic Agents / pharmacology
  • Cyclooxygenase 2 / biosynthesis*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry / methods
  • Lymphoma, Non-Hodgkin / metabolism*
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / biosynthesis
  • Neoplasm Proteins / biosynthesis

Substances

  • ABCC2 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Cyclooxygenase 2
  • multidrug resistance-associated protein 1