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)
Increased expression of
P-glycoprotein
encoded by the mdr-1 gene is a well-characterised mechanism for resistance to cancer chemotherapeutic drugs in cell lines. However, the
P-glycoprotein
expression after removal of the selection pressure has not fully been elucidated. The stability of
P-glycoprotein
expression in the presence (+) and absence (-) of vincristine (30 or 150 nM) was studied in multidrug resistant K562 cell lines (VCR30+, VCR150+, VCR30- and VCR150-) for 11 months. The
P-glycoprotein
protein and mdr-1 mRNA levels were determined at regular intervals using flow cytometry and real-time PCR, respectively. Chemosensitivity to a panel of antineoplastic drugs was measured using an MTT assay. The presence of vincristine (VCR30+ and VCR150+) resulted in high and stable levels of
P-glycoprotein
and mdr-1 mRNA during the whole period compared to wild type. As for the VCR30- and VCR150- subcultures, the expressions of
P-glycoprotein
and mdr-1 mRNA were stable for five months, and then the levels decreased rapidly. Concomitantly, the sensitivity to drugs known as
P-glycoprotein
substrates was restored. In conclusion, resistant cells growing in the presence of the inducing drug have a stable
P-glycoprotein
expression and resistance level, but removing the inducing drug may result in a sudden and rapid lowering of
P-glycoprotein
and mdr-1 mRNA levels as long as five months after
drug withdrawal
.
...
PMID:Spontaneous reversal of p-glycoprotein expression in multidrug resistant cell lines. 1467 64
