Aspirin enhances multidrug resistance gene 1 expression in human Molt-4 T lymphoma cells.
BACKGROUND
We recently found that aspirin induces the expression of P-glycoprotein (P-gp), a protein mediating drug resistance, in human prostate cancer cells. The purpose of this study was to evaluate the effect of aspirin on the expression of P-gp in a different human cancer type, i.e., T lymphoma. Furthermore, we analyzed this effect at the level of the gene encoding P-gp, MDR1, and of the transcription factor (NF-IL6), regulating this gene.


METHODS
NF-IL6 was assayed by the electrophoretic mobility shift assay, MDR1 mRNA was assayed by the reverse transcriptase polymerase chain reaction (RT-PCR), and P-gp was assayed by Western blotting.


RESULTS
aspirin, at plasma attainable levels, induced NF-IL6 DNA-binding activity, and increased MDR1 mRNA expression (by up to 140%), as well as the expression of P-gp, in Molt-4 cells.


CONCLUSIONS
This study suggests that treatment with aspirin induces a cellular signal culminating in the enhancement of P-gp expression in T lymphoma Molt-4 cells.
Flescher
E
E
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 69978. flascher@post.tau.ac.il
Rotem
R
R
Kwon
P
P
Azare
J
J
Jaspers
I
I
Cohen
D
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D019450:Genes, MDR / Q000187:drug effects*; D006801:Humans; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000894:Anti-Inflammatory Agents, Non-Steroidal; D022782:CCAAT-Enhancer-Binding Protein-beta; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D001241:Aspirin