About: Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells     Goto   Sponge   NotDistinct   Permalink

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Description
  • The effect of ABCB1 and ABCG2 expressions on cell resistance to daunorubicin (DRN), imatinib, and nilotinib was studied in human leukemia cells. We used a set of cells derived from a parental K562 cell line, expressing various levels of ABCB1 and ABCG2, respectively. We observed that the resistance to DRN and imatinib was proportional to the expression level of ABCB1. Similarly, the resistance to nilotinib and imatinib was proportional to the expression level of ABCG2. Importantly, K562/DoxDR05 and K562/ABCG2-Z cells with the lowest expressions of ABCB1 and ABCG2, respectively, failed to reduce the intracellular levels of imatinib to provide a significant resistance to this drug. However, the K562/DoxDR05 and K562/ABCG2-Z cells significantly decreased the intracellular levels of DRN and nilotinib, respectively, thereby mediating significant resistances to these drugs. Our results clearly indicated that resistance to anticancer drugs mediated by main ABC transporters, ABCB1 and ABCG2, strongly depends on their expressions at protein levels. Importantly, resistance for one drug might be maintained while resistance for other ones might become undetectable at low transporter expression levels.
  • The effect of ABCB1 and ABCG2 expressions on cell resistance to daunorubicin (DRN), imatinib, and nilotinib was studied in human leukemia cells. We used a set of cells derived from a parental K562 cell line, expressing various levels of ABCB1 and ABCG2, respectively. We observed that the resistance to DRN and imatinib was proportional to the expression level of ABCB1. Similarly, the resistance to nilotinib and imatinib was proportional to the expression level of ABCG2. Importantly, K562/DoxDR05 and K562/ABCG2-Z cells with the lowest expressions of ABCB1 and ABCG2, respectively, failed to reduce the intracellular levels of imatinib to provide a significant resistance to this drug. However, the K562/DoxDR05 and K562/ABCG2-Z cells significantly decreased the intracellular levels of DRN and nilotinib, respectively, thereby mediating significant resistances to these drugs. Our results clearly indicated that resistance to anticancer drugs mediated by main ABC transporters, ABCB1 and ABCG2, strongly depends on their expressions at protein levels. Importantly, resistance for one drug might be maintained while resistance for other ones might become undetectable at low transporter expression levels. (en)
Title
  • Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells
  • Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells (en)
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  • Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells
  • Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells (en)
skos:notation
  • RIV/61989592:15110/14:33151310!RIV15-MSM-15110___
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  • 42437
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  • RIV/61989592:15110/14:33151310
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  • Bcr-Abl tyrosine kinase; Intracellular drug level; Drug resistance; K562 cells; Tyrosine kinase inhibitors; ABC transporters (en)
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  • [8024648292E4]
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  • 219
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  • Doležel, Petr
  • Mlejnek, Petr
  • Kosztyu, Petr
  • Bukvová, Romana
http://linked.open...ain/vavai/riv/wos
  • 000345637600023
issn
  • 0009-2797
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.cbi.2014.06.009
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  • 15110
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