Abstract
Multidrug resistance (MDR) and multi-organ infiltration are the major obstacles to the successful treatment of leukemia. It is known that the drug efflux protein, P-glycoprotein (P-gp), and inhibitors of apoptosis proteins (IAPs) are involved in the MDR of leukemic cells, but their roles in leukemia infiltration have not been clearly elucidated. In this study, leukemic cell lines K562 and HL60 and their MDR variants K562R and HL60R have been used to analyze their infiltrative ability. MDR variants display enhanced invasion compared with parental cells. Results from xenografts in SCID (severe combined immunodeficiancy) mice are consistent with these in vitro observations. Furthermore, P-gp and cIAP are overexpressed and co-localize with protein kinase C-ε (PKC-ε) in MDR variants. Our study shows that overexpression of P-gp and cIAP may enhance the infiltration of leukemic cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Animals
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Movement / genetics
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Doxorubicin / pharmacology
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Drug Resistance, Neoplasm / genetics*
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Gene Expression Regulation, Leukemic
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Gene Expression*
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HL-60 Cells
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Humans
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Inhibitor of Apoptosis Proteins / genetics
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Inhibitor of Apoptosis Proteins / metabolism*
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K562 Cells
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Leukemia* / genetics
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Leukemia* / metabolism
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Mice
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Mice, SCID
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Neoplasm Invasiveness / genetics*
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Protein Binding
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Protein Kinase C-epsilon / metabolism
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Protein Transport / physiology
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Up-Regulation
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Xenograft Model Antitumor Assays
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents
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Inhibitor of Apoptosis Proteins
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Doxorubicin
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Protein Kinase C-epsilon