[The role of Src kinase inhibitor ZD6474 on multi-drug resistant K562/A02 cells].
OBJECTIVE
To investigate the role of Src kinase inhibitor ZD6474 on the growth of multidrug-resistant K562/A02 cells and its regulatory mechanisms.


METHODS
The possible mechanisms of drug-resistance were tested by Western blot. Proliferation assays and cell cycle distribution were analyzed by WST metric analysis. Western blot were used to investigate the mechanisms of antiproliferative activity induced by tyrosine kinase inhibitor ZD6474. The in vivo anti-tumor activity was evaluated in K562, K562/A02 xenografted nude mice by administration of ZD6474 (25 - 100 mg×kg(-1)×d(-1), PO).


RESULTS
Compared with parental K562 cells, marked high levels of p-Src and Src expression were detected in K562/A02 cells. WST results showed that the IC(50) values of ZD6474 on K562 and K562/A02 after 48 hours incubation were (1.61 ± 0.07) µmol/L and (3.22 ± 0.21)µmol/L, respectively. ZD6474 caused an accumulation of cells in the G(0)/G(1) fraction and apoptosis by inhibiting the expressions of p-Src and Src kinase. Administration of ZD6474 produced a dose-dependent inhibition of tumor growth. 50 mg/kg ZD6474 produced the growth inhibition rates of 43.7% and 56.3%, respectively in K562 and K562/A02.


CONCLUSIONS
Our results indicated that inhibiting Src kinase could induce K562/A02 cells apoptosis in vitro and in vivo.
Department of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
Hong-yun
HY
Jia
Juan
J
Li
Zhong-ying
ZY
Wang
Qiang
Q
Zhou
Xiao-man
XM
Wu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D010880:Piperidines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
D010880:Piperidines; D011799:Quinazolines; D019061:src-Family Kinases; C452423:vandetanib