Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL-60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells.

Abstract:

:The present study selected and characterized a multidrug-resistant HL-60 human acute promyelocytic leukemia cell line, HL-60/RS, by exposure to stepwise incremental doses of doxorubicin. The drug-resistant HL-60/RS cells exhibited 85.68-fold resistance to doxorubicin and were cross-resistant to other chemotherapeutics, including cisplatin, daunorubicin, cytarabine, vincristine and etoposide. The cells over-expressed the transporters P-glycoprotein, multidrug-resistance-related protein 1 and breast-cancer-resistance protein, encoded by the adenosine triphosphate-binding cassette (ABC)B1, ABCC1 and ABCG2 genes, respectively. Unlike other recognized chemoresistant leukemia cell lines, HL-60/RS cells were also strongly cross-resistant to arsenic trioxide. The proportion of leukemia stem cells (LSCs) increased synchronously with increased of drug resistance in the doxorubicin-induced HL-60 cell population. The present study confirmed that doxorubicin-induced HL-60 cells exhibited multidrug-resistance and high arsenic-trioxide resistance. Drug-resistance in these cells may be due to surviving chemoresistant LSCs in the HL-60 population, which have been subjected to long and consecutive selection by doxorubicin.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Chen J,Wei H,Cheng J,Xie B,Wang B,Yi J,Tian B,Liu Z,Wang F,Zhang Z

doi

10.3892/ol.2017.7353

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

1255-1262

issue

1

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-7353

journal_volume

15

pub_type

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