Study of CYP3A5 in drug resistance mechanisms in acute leukemia / 中华血液学杂志
Chinese Journal of Hematology
; (12): 286-289, 2003.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-354892
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate if CYP3A5 is involved in drug resistances mechanisms of acute leukemia.</p><p><b>METHODS</b>By using RT-PCR, immunohistochemistry and MTT assay, CYP3A5 mRNA and protein were detected in leukemia cell lines and acute leukemia patients, meanwhile transcriptional regulation of CYP3A5 induced by daunorubicin was observed. A pcDNA3-CYP3A5 reconstituted plasmid and its stably transfected cell line HL-60/CYP3A5 were both established.</p><p><b>RESULTS</b>CYP3A5 mRNA was detected in K562 and U937 cells, whose IC(50) values of daunorubicin were 2.1-fold higher than those of NB4 and HL-60 cells. Bone marrow CYP3A5 positive blast cell percentage at the time of diagnosis in primary drug resistance group (17.2%) was significantly higher than that of continuous complete remission (CCR) group (0.4%) and secondary drug resistance group (5.4%). In their first complete remission of the early relapsed group, the positive rate had been 23.9% as compared with that of CCR group (1.3%). Daunorubicin increased CYP3A5 mRNA level in K562/A02 and activated its transcription in HL-60/ADR. HL-60/CYP3A5 cell was significantly resistant to daunorubicin and vincristine than HL-60 cells did (3.0 and 4.0 times, respectively).</p><p><b>CONCLUSION</b>CYP3A5 expressed in leukemia cells may cause in situ metabolization of many kinds of anticancer drugs, thus led to drug resistance.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Fisiologia
/
RNA Mensageiro
/
Células Tumorais Cultivadas
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Leucemia
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Daunorrubicina
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Resistencia a Medicamentos Antineoplásicos
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Sistema Enzimático do Citocromo P-450
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Tratamento Farmacológico
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Citocromo P-450 CYP3A
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Hematology
Ano de publicação:
2003
Tipo de documento:
Artigo