[The reverse effect on drug-resistance against tyrosine kinase inhibitor STI571 in mdr1 and bcr-abl positive leukemic cells].
To explore the possibility of leukemia cell line of both bcr-abl and mdr-1 positive were cross-resistant to tyrosine kinase inhibitor STI571 and its reversal way, the inhibitory effect of STI571 on K562-n/VCR cells was detected with MTT method and reverse effects of CsA, TAM, IFN-alpha and CsA cominated with IFN-alpha were observed. The results showed that K562-n/VCR cell line expressing bcr-abl and mdr1 positive was resistant to STI571, and could be reversed by 5.18, 1.82 and 1.67-fold respectively, when treated with CsA, TAM, and IFN-alpha. It could be reversed by 34.87-fold with combination of half-dose CsA and IFN-alpha. In conclusion, amplification of mdr1 gene may contribute to drug-resistance of bcr-abl positive leukemic cells against STI571. The reversal agents, CsA, TAM and IFN-alpha show obviously reverse effects on drug-resistance. The combination of half-dose of both CsA and IFN-alpha display stronger effect than the full dose of either.
Chen
Li
L
Department of Hematology, Changhai Hospital of The Second Military Medical University, Shanghai 200433, China.
Wang
Jian-Min
JM
Xu
Xiao-Ping
XP
Gao
Lei
L
Fei
Xin-Hong
XH
Lou
Jing-Wei
JW
Huang
Zheng-Xia
ZX
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D016572:Cyclosporine / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D019450:Genes, MDR; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000494:pharmacology; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology
D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D013629:Tamoxifen; D016572:Cyclosporine; D000068877:Imatinib Mesylate