Establishment of Drug-resistant Acute Lymphoblastic Leukemic Cell Lines and Their Resistance Mechanism.

Tian-tian LI; Li Zhang; Shan-dong Tao; Jing-jing MA; Liang YU

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Establishment of Drug-resistant Acute Lymphoblastic Leukemic Cell Lines and Their Resistance Mechanism.

Author: Tian-Tian LI ^{1
,

2} ; Li ZHANG ^{1
,

2} ; Shan-Dong TAO ^{1
,

2} ; Jing-Jing MA ^{1
,

2} ; Liang YU ^{1
,

3}
Author Information

1. Department of Hematology, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an 223300, Jiangsu Province, China
2. Key Laboratory of Hematology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
3. Key Laboratory of Hematology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. E-mail: yuliangha@163.com.
Publication Type:Journal Article
MeSH: ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line; Cytarabine; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Precursor Cell Lymphoblastic Leukemia-Lymphoma
From: Journal of Experimental Hematology 2018;26(3):698-704
CountryChina
Language:Chinese
Abstract:
OBJECTIVETo establish the adriamycin(ADR)-resistant ALL cell lines and to investigate their drug-resistan mechanisms.
METHODSThe drug-resistant cell lines SUP-B15/ADR and RS4;11/ADR were derived by exposing the parental cells [SUP-B15(Ph) and RS4;11(Ph)] to the ascending concentrations of ADR. The cell viability was detected by CCK-8 method. The expression of P-gp was examined by Western blot, and RT-qPCR was performed to detect the expression of MDR1.
RESULTSThe drug-resistant cell lines SUP-B15/ADR and RS4;11/ADR were successfully established, their resistance indexes were 14.088±0.763 and 10.473±1.024, respectively. After the cryopreserved SUP-B15/ADR and RS4;11/ADR cells were resuscitated, their survival rates were 88.4±1.2% and 89.3±1.6% respectively, while their resistance indexes were 13.976±0.967 and 10.342±0.846 respectively (P>0.05). When the drug-resistant cells were cultured in the medium without ADR for 1 month, their drug-resistance indexes dropped down to 12.893±1.255 and 9.327±0.321 respectively(P<0.05). Drug-resistant cell lines had the cross-resistance to cytarabine and etoposide. The expression of P-gp and MDR1 in drug-resistant cells was significantly higher than that in wild-type cells.
CONCLUSIONTwo drug-resistant ALL cell lines have been successfully established by exposing to the ascending concentration of ADR. The over-expression of MDR1 and P-gp in drug-resistant cells may be one of the mechanisms underlying the drug resistance.