Spontaneous Reversal of P-Glycoprotein Expression in Multidrug Resistant Cell Lines
2003 (English)In: Pharmacology and Toxicology, ISSN 0901-9928, Vol. 93, no 6, 297-304 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2003. Vol. 93, no 6, 297-304 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-46413DOI: 10.1111/j.1600-0773.2003.pto930608.xOAI: oai:DiVA.org:liu-46413DiVA: diva2:267309
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.
Postprint available at: Linköping University Electronic Press