Open Access
Article
Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity
Jinqing Tang1,Xiaotian Xie1,*,Xiaoping Zhang2,Xiaohong Qiao1,Shayi Jiang1,Wei Shi1,Yuexia Shao1,Xiaoxun Zhou1
1
Department of Pediatrics, Tongji Hospital, Tongji University school of medicine, Shanghai 200065, China
2
Department of Nuclear Medicine, Shanghai tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
DOI: 10.2741/3944 Volume 17 Issue 2, pp.569-574
Published: 01 January 2012
(This article belongs to the Special Issue Pathogenesis and diagnostic modalities in cancer)
*Corresponding Author(s):  
Xiaotian Xie
E-mail:  
xiaotianxie@yeah.net
Abstract

Cytarabine (araC) is a highly active antimetabolite against hematological malignancy while the agent shows limited activity for some patients despite maintenance or continued therapy with ara-C-containing regiments. In this study, we focused to elucidate the mechanism of intrinsic resistance to araC. The concentration of intracellular ara-CTP and incorporated ara-CTP were monitored in human leukemia cell line-HL-60 for different passages in parental with its variant HL-60R. The expression of mRNA for deoxycytidine kinase (dCK), cytidine deaminas (CDA), human equilibrative nucleoside transporter 1 (hENT1), and cytosolic 50-nucleotidase II (cN-II) were examined by Real-time PCR in HL-60 and HL-60R for different passages. And activities of two metabolizing enzymes for araC, dCK and CDA were further examined. The results showed that the concentration of intracellular ara-CTP was significantly reduced and the ara-U increased in HL-60 cells for 50 passages compared with the 5 passages, and associated with higher CDA activity. All the factors in HL-60R cells did not change by the incubation of ara-C. In conclusion, the long term cultured cells are intrinsically resistant to ara-C through high CDA activity, but not low DCK activity.

Key words

Cytarabine; HL-60; CDA Activity; Leukemic Cells

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Jinqing Tang, Xiaotian Xie, Xiaoping Zhang, Xiaohong Qiao, Shayi Jiang, Wei Shi, Yuexia Shao, Xiaoxun Zhou. Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity. Frontiers in Bioscience-Landmark. 2012. 17(2); 569-574.