Aldehyde-dehydrogenase gene-transduced hematopoietic cell line K562 overcomes the cytoxicity of cyclophosphamide in vitro / 中国实验血液学杂志
Journal of Experimental Hematology
;
(6): 205-208, 2002.
Article
in English
| WPRIM
| ID: wpr-337609
ABSTRACT
The identification of genes inducing resistance to anticancer chemotherapeutic agents and their introduction into hematopoietic cells represents a promising approach to overcome bone marrow toxicity, the limiting factor for most high-dose chemotherapy regimens. Because resistance to cyclophosphamide has been correlated with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in tumor cells lines in vitro, this study tested whether ALDH1 overexpression could directly induce cyclophosphamide resistance. Results showed that a retroviral vector was used to transduce full-length human ALDH1 cDNA into human hematopoietic cell line K562 that was then tested for resistance to 4-hydroxycyclophosphamide (4-HC), an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted in a significant increases in cyclophosphamide resistance in transduced K562 cells (50% inhibition concentration, IC50 = 10 micro mol/L). These findings indicate that ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro and provide a basis for testing the efficacy of ALDH1 gene transduction to protect bone marrow cells from high-dose cyclophosphamide in vivo.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Retroviridae
/
Transfection
/
Gene Expression Regulation, Enzymologic
/
Cell Division
/
Cell Survival
/
Drug Resistance, Neoplasm
/
Antineoplastic Agents, Alkylating
/
K562 Cells
/
Inhibitory Concentration 50
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Journal of Experimental Hematology
Year:
2002
Type:
Article
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