Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells

Xing Xiang Peng; Zhi Shi; Amit K. Tiwari; Vijaya L. Damaraju; Liwu Fu; Carol E. Cass; Charles R. Ashby; Gary D. Kruh; Zhe Sheng Chen

doi:10.3892/ol.2011.288

Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells

Xing Xiang Peng
, Zhi Shi
, Amit K. Tiwari
, Vijaya L. Damaraju
, Liwu Fu
, Carol E. Cass
, Charles R. Ashby
, Gary D. Kruh
, Zhe Sheng Chen

St. John's University
New York University
Sun Yat-Sen University
University of Alberta
University of Illinois at Chicago

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

To investigate the mechanisms of cellular resistance to 6-mercaptopurine (6-MP) in chronic myeloid leukemia (CML), a 6-MP resistant cell line (K562-MP5) was established by stepwise selection of the CML cell line (K562). The results of the drug sensitivity analysis of the K562-MP5 cell line revealed the cells to be 339-fold more resistant to 6-MP compared with the parental K562 cells. K562-MP5 cells exhibited decreased accumulation and increased efflux of [¹⁴C]6-MP and its metabolites. In addition, K562-MP5 cells showed increased [³H]MTX transport. K562-MP5 cells over--expressed P-glycoprotein (P-gp) and up-regulated MDR1 mRNA levels. Taken together, these results suggest that the up-regulation of P-gp, which contributes to the decreased accumulation by increasing the efflux of 6-MP and its metabolites, underlies the mechanism of 6-MP resistance in K562 cells.

Original language	English
Pages (from-to)	549-556
Number of pages	8
Journal	Oncology Letters
Volume	2
Issue number	3
DOIs	https://doi.org/10.3892/ol.2011.288
State	Published - May 2011
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

6-mercaptopurine
ATP binding cassette transporter
Chronic myeloid leukemia
Multidrug resistance
P-glycoprotein

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10.3892/ol.2011.288

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@article{9862d6aa13864766b7ba1ccc0a8d948b,

title = "Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells",

abstract = "To investigate the mechanisms of cellular resistance to 6-mercaptopurine (6-MP) in chronic myeloid leukemia (CML), a 6-MP resistant cell line (K562-MP5) was established by stepwise selection of the CML cell line (K562). The results of the drug sensitivity analysis of the K562-MP5 cell line revealed the cells to be 339-fold more resistant to 6-MP compared with the parental K562 cells. K562-MP5 cells exhibited decreased accumulation and increased efflux of [14C]6-MP and its metabolites. In addition, K562-MP5 cells showed increased [3H]MTX transport. K562-MP5 cells over--expressed P-glycoprotein (P-gp) and up-regulated MDR1 mRNA levels. Taken together, these results suggest that the up-regulation of P-gp, which contributes to the decreased accumulation by increasing the efflux of 6-MP and its metabolites, underlies the mechanism of 6-MP resistance in K562 cells.",

keywords = "6-mercaptopurine, ATP binding cassette transporter, Chronic myeloid leukemia, Multidrug resistance, P-glycoprotein",

author = "Peng, \{Xing Xiang\} and Zhi Shi and Tiwari, \{Amit K.\} and Damaraju, \{Vijaya L.\} and Liwu Fu and Cass, \{Carol E.\} and Ashby, \{Charles R.\} and Kruh, \{Gary D.\} and Chen, \{Zhe Sheng\}",

year = "2011",

month = may,

doi = "10.3892/ol.2011.288",

language = "English",

volume = "2",

pages = "549--556",

journal = "Oncology Letters",

issn = "1792-1074",

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number = "3",

}

TY - JOUR

T1 - Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells

AU - Peng, Xing Xiang

AU - Shi, Zhi

AU - Tiwari, Amit K.

AU - Damaraju, Vijaya L.

AU - Fu, Liwu

AU - Cass, Carol E.

AU - Ashby, Charles R.

AU - Kruh, Gary D.

AU - Chen, Zhe Sheng

PY - 2011/5

Y1 - 2011/5

N2 - To investigate the mechanisms of cellular resistance to 6-mercaptopurine (6-MP) in chronic myeloid leukemia (CML), a 6-MP resistant cell line (K562-MP5) was established by stepwise selection of the CML cell line (K562). The results of the drug sensitivity analysis of the K562-MP5 cell line revealed the cells to be 339-fold more resistant to 6-MP compared with the parental K562 cells. K562-MP5 cells exhibited decreased accumulation and increased efflux of [14C]6-MP and its metabolites. In addition, K562-MP5 cells showed increased [3H]MTX transport. K562-MP5 cells over--expressed P-glycoprotein (P-gp) and up-regulated MDR1 mRNA levels. Taken together, these results suggest that the up-regulation of P-gp, which contributes to the decreased accumulation by increasing the efflux of 6-MP and its metabolites, underlies the mechanism of 6-MP resistance in K562 cells.

AB - To investigate the mechanisms of cellular resistance to 6-mercaptopurine (6-MP) in chronic myeloid leukemia (CML), a 6-MP resistant cell line (K562-MP5) was established by stepwise selection of the CML cell line (K562). The results of the drug sensitivity analysis of the K562-MP5 cell line revealed the cells to be 339-fold more resistant to 6-MP compared with the parental K562 cells. K562-MP5 cells exhibited decreased accumulation and increased efflux of [14C]6-MP and its metabolites. In addition, K562-MP5 cells showed increased [3H]MTX transport. K562-MP5 cells over--expressed P-glycoprotein (P-gp) and up-regulated MDR1 mRNA levels. Taken together, these results suggest that the up-regulation of P-gp, which contributes to the decreased accumulation by increasing the efflux of 6-MP and its metabolites, underlies the mechanism of 6-MP resistance in K562 cells.

KW - 6-mercaptopurine

KW - ATP binding cassette transporter

KW - Chronic myeloid leukemia

KW - Multidrug resistance

KW - P-glycoprotein

UR - https://www.scopus.com/pages/publications/79953286779

U2 - 10.3892/ol.2011.288

DO - 10.3892/ol.2011.288

M3 - Article

AN - SCOPUS:79953286779

SN - 1792-1074

VL - 2

SP - 549

EP - 556

JO - Oncology Letters

JF - Oncology Letters

IS - 3

ER -

Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells

Abstract

UN SDGs

Keywords

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