Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Multidrug resistance (MDR) of leukemia cells is a major obstacle in chemotherapeutic treatment. The high expression and constitutive activation of
P-glycoprotein
(
P-gp
) and multidrug resistance protein-1 (MRP-1) have been reported to play a vital role in enhancing cell resistance to anticancer drugs in many tumors. The present study aimed to investigate the reversal of MDR by silencing
homeobox A10
(
HOXA10
) in adriamycin (ADR)-resistant human chronic myelogenous leukemia (CML) K562/ADM cells by modulating the expression of
P-gp
and MRP-1. K562/ADM cells were stably transfected with
HOXA10
-targeted short hairpin RNA (shRNA). The results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis showed that the mRNA and protein expression of
HOXA10
was markedly suppressed following transfection with a shRNA-containing vector. The sensitivity of the K562/ADM cells to ADR was enhanced by the silencing of
HOXA10
, due to the increased intracellular accumulation of ADR. The accumulation of ADR induced by the silencing of
HOXA10
may be due to the downregulation of
P-gp
and MRP-1. Western blot analysis revealed that downregulating
HOXA10
inhibited the protein expression of
P-gp
and MRP-1. Taken together, these results suggest that knockdown of
HOXA10
combats resistance and that
HOXA10
is a potential target for resistant human CML.
...
PMID:Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1. 2703 4
