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Spontaneous Reversal of P-Glycoprotein Expression in Multidrug Resistant Cell Lines
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi.
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi.
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi.
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
2003 (engelsk)Inngår i: Pharmacology and Toxicology, ISSN 0901-9928, E-ISSN 1600-0773, Vol. 93, nr 6, s. 297-304Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

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2003. Vol. 93, nr 6, s. 297-304
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URN: urn:nbn:se:liu:diva-46413DOI: 10.1111/j.1600-0773.2003.pto930608.xOAI: oai:DiVA.org:liu-46413DiVA, id: diva2:267309
Merknad
The definitive version is available at www.blackwell-synergy.com: Henrik Green, Kourosh Lotfi, Anna Lena Zackrisson and Curt Peterson, Spontaneous Reversal of P-Glycoprotein Expression in Multidrug Resistant Cell Lines, 2003, Pharmacology and Toxicology, (93), 6, 297-304. http://dx.doi.org/10.1111/j.1600-0773.2003.pto930608.x Postprint available at: Linköping University Electronic Press http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-46413 Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13

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