[Establishment of K562 cell lines resistant to STI571 and a preliminary biological study].
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.
Gao
Lei
L
Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
Wang
Jian-Min
JM
Xu
Xiao-Ping
XP
Chen
Li
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D019450:Genes, MDR; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate