Establishment of K562 cell lines resistant to STI571 and a preliminary biological study.
- Author:
Lei GAO
1
;
Jian-Min WANG
;
Xiao-Ping XU
;
Li CHEN
Author Information
1. Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
pharmacology;
Benzamides;
Cell Cycle;
drug effects;
Cell Proliferation;
drug effects;
Drug Resistance, Neoplasm;
Genes, MDR;
Humans;
Imatinib Mesylate;
K562 Cells;
Piperazines;
pharmacology;
Pyrimidines;
pharmacology;
RNA, Messenger;
analysis
- From:
Journal of Experimental Hematology
2004;12(5):584-589
- CountryChina
- Language:Chinese
-
Abstract:
To produce leukemic STI571-resistant cell lines and to explore the molecular mechanism of STI571-resistance, cell lines K562-n and K562-n/VCR were induced by exposing cells to gradually increasing STI571 concentration of culture medium to have STI571-resistance and major biological characteristics between these subclones and the parent cells were compared. The results showed that a STI571-resistant cell line based on multidrug-resistance was established, which exhibited 23.41-fold resistance to STI571, 662.26-fold resistance to VCR and cross-resistance to HHT. K562-n/STI was generated from K562-n and had some characteristics of MDR. The intracellular accumulation of DNR in K562-n/STI and K562-n/VCR/STI were 33.24 and 18.76 respectively. Transcription of mdr-1 gene in both K562-n/STI and K562-n/VCR/STI was positive. Cell doubling time of K562-n/STI and K562-n/VCR/STI was significantly longer than that in their parent cells (P <0.05). And proliferation index was also higher than that in parent cells (P <0.05). It is conclusion that the tolerance of K562-n cells to STI571 can be augmented by adding low-dose of STI571 into the culture medium repeatedly. K562-n/STIs expressed MDR at some extent, and transcription of mdr-1 gene in K562-n/STIs was positive. As K562-n is a cell line used to develop human leukemia in nude mice, K562-n/STI and K562-n/VCR/STI 571 will contribute to the study of mechanism of STI571-resistance as in vitro and in vivo experimental models.
