Aldehyde-dehydrogenase gene-transduced hematopoietic cell line K562 overcomes the cytoxicity of cyclophosphamide in vitro.
- Author:
Xiao-Wei YANG
1
;
Wei WANG
;
Jian-Xin FU
;
Jian-Nong CEN
;
Feng GUO
;
Xue-Ming XIA
;
Zi-Xing CHEN
Author Information
1. Jiangsu Institue of Hematology, The First Affiliated Hospital of Suzhou University, Suzhou 215006, China.
- Publication Type:Journal Article
- MeSH:
Aldehyde Dehydrogenase;
genetics;
Antineoplastic Agents, Alkylating;
pharmacology;
Cell Division;
drug effects;
Cell Survival;
drug effects;
Cyclophosphamide;
analogs & derivatives;
pharmacology;
Dose-Response Relationship, Drug;
Drug Resistance, Neoplasm;
Gene Expression Regulation, Enzymologic;
Genetic Vectors;
genetics;
Humans;
Inhibitory Concentration 50;
K562 Cells;
drug effects;
enzymology;
metabolism;
Retroviridae;
genetics;
Transfection
- From:
Journal of Experimental Hematology
2002;10(3):205-208
- CountryChina
- Language:English
-
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.
