Increased ABCB1 expression in TP-110-resistant RPMI-8226 cells.

Abstract

TP-110, a novel proteasome inhibitor, has been found to possess potent growth inhibition in human multiple myeloma cells. To enhance its therapeutic effects, we established TP-110-resistant RPMI-8226 (RPMI-8226/TP-110) cells and elucidated their resistance mechanisms. The IC₅₀ value for TP-110 cytotoxicity in the RPMI-8226/TP-110 cells was about 10-fold higher than that of the parental sensitive cells. The RPMI-8226/TP-110 cells exhibited distinct drug resistance to other proteasome inhibitors. Furthermore, they showed high cross-resistance to the cytotoxic effects of doxorubicin, etoposide, taxol, and vincristine. P-glycoprotein (MDR1), encoded by ABCB1, was elevated in the RPMI-8226/TP-110 cells, and the MDR1 inhibitor verapamil overcame their resistance to TP-110. The results of DNA microarray and RT-PCR suggested that the expression of ABCB1 is significantly elevated in RPMI-8226/TP-110 cells. This indicates that resistance in RPMI-8226/TP-110 cells is involved in the expression of P-glycoprotein, a drug-efflux pump.

• Authors: Masatomi Iijima, Isao Momose, Daishiro Ikeda
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 74 Issue 9 Pg. 1913-9 ( 2010) ISSN: 1347-6947 [Electronic] England
• PMID: 20834157 (Publication Type: Journal Article)

Chemical References

• 1-naphthylacetyl-(O-methyl)-tyrosyl-valyl-(O-methyl)-tyrosinal
• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Oligopeptides
• Proteasome Inhibitors
• Verapamil

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (analysis, biosynthesis)
• Antineoplastic Agents (pharmacology)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Inhibitory Concentration 50
• Multiple Myeloma (chemistry, drug therapy, metabolism)
• Oligopeptides (pharmacology)
• Proteasome Inhibitors
• Tumor Cells, Cultured
• Verapamil (pharmacology)