[Multidrug resistance mechanisms in cell line HL-60/VCR].
OBJECTIVE
Drug resistance is a major factor in chemotherapeutic failure of leukemia. Multidrug resistant cell lines are the good models for investigating the mechanisms and reversal of acquired drug resistance. This study was designed to explore the multidrug resistance (MDR) mechanisms in cell line HL-60/VCR.


METHODS
Flow cytometry and a panel of antibodies were used to analyze the expression of MDR proteins (P-gp, MRP, LRP, BCRP, GST-pi) and apoptosis-modulating proteins (bcl-2, bcl-x, bax, bad) in MDR cell line HL-60/VCR and drug sensitive cell line HL-60.


RESULTS
The expression levels of MDR proteins (P-gp, MRP, BCRP, GST-pi) were (18.62, 1.19, 1.50, 1.32-flod) higher in HL-60/VCR than in HL-60, while the expression of LRP level was similar. The levels of apoptosis-modulating proteins(bcl-2, bcl-x, bad) were (2.48, 1.25, 1.08-fold) higher in HL-60/VCR than in HL-60, while the pro-apoptosis protein bax contrarily decreased in HL-60/VCR.


CONCLUSIONS
Various MDR mechanisms were involved in multi-drug resistance HL-60/VCR cell line, which including increasing expression of drug-resistance protein (P-gp, MRP, BCRP, and GST-pi); the apoptosis-modulating proteins (bcl-2, bcl-x, bax, and bad) might take part in the mechanism of drug resistance.
Zhu
Xing-hu
XH
Department of Hematology, First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou 215006, P. R. China.
Li
Jian-yong
JY
Xia
Xue-ming
XM
Zhu
Ming-qing
MQ
Geng
Mei-ju
MJ
Chen
Li
L
Zhang
Jin-qi
JQ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; C494819:BAD protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D002352:Carrier Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D014750:Vincristine; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase