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Spontaneous Reversa...
Spontaneous Reversal of P-Glycoprotein Expression in Multidrug Resistant Cell Lines
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- Green, Henrik (författare)
- Linköpings universitet,Hälsouniversitetet,Klinisk farmakologi
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- Lotfi, Kourosh (författare)
- Linköpings universitet,Hälsouniversitetet,Klinisk farmakologi
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- Zackrisson, Anna Lena (författare)
- Linköpings universitet,Hälsouniversitetet,Klinisk farmakologi
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- Peterson, Curt (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Klinisk farmakologi,Onkologiska kliniken US
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(creator_code:org_t)
- Wiley, 2003
- 2003
- Engelska.
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 93:6, s. 297-304
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Nyckelord
- MEDICINE
- MEDICIN
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