Cross-resistance to cytosine arabinoside in human acute myeloid leukemia cells selected for resistance to vincristine.
OBJECTIVE
The goals of the study were to reveal the involvement of P-glycoprotein (P-gp), the product of multidrug resistance 1 gene (MDR1) in cellular resistance to vincristine (VCR) and investigate cross-resistance against cytosine arabinoside (Ara-C) in HL60 and HL60/VCR cell lines.


METHODS
HL60 cells (human acute myeloid leukemia cell line) were cultured on medium with 1-50 nM of VCR for 4-6 weeks, and VCR resistant cells (HL60/VCR) were selected. The viability of cells was assessed by MTT assay and the expression of MDR1 gene was detected by RT-PCR.


RESULTS
No expression of MDR1 gene was revealed in HL60 cells, but MDR1 started to be expressed after incubation of cells with 2 nM of VCR and its expression level elevates with increase of agent concentration. MTT test has shown that HL-60/VCR cells were 75-fold more resistant to VCR and 42-fold higher resistant to cytosine arabinoside (Ara-C) compared to sensitive HL60 cells.


CONCLUSIONS
Aquired resistance to VCR and cross-resistance to Ara-C correlates with MDR1 gene expression in vitro.
Baran
Y
Y
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey. ybaran@metu.edu.tr
Gunduz
U
U
Ural
A U
AU
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000208:Acute Disease; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D012641:Selection, Genetic; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003561:Cytarabine; D014750:Vincristine