Positive correlation between cyclooxygenase-2 and ABC-transporter expression in non-Hodgkin's lymphomas.
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.
Szczuraszek
Katarzyna
K
Department of Histology and Embryology, University School of Medicine, Wroclaw, Poland.
Materna
Verena
V
Halon
Agnieszka
A
Mazur
Grzegorz
G
Wróbel
Tomasz
T
Kuliczkowski
Kazimierz
K
Maciejczyk
Adam
A
Zabel
Maciej
M
Drag
Marcin
M
Dietel
Manfred
M
Lage
Hermann
H
Surowiak
Pawel
P
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D051546:Cyclooxygenase 2; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1