Homoharringtonine contributes to imatinib sensitivity in chronic myeloid leukemia cell lines / 中国肿瘤临床
Chinese Journal of Clinical Oncology
;
(24): 1017-1020, 2014.
Artigo
em Chinês
| WPRIM
| ID: wpr-456504
ABSTRACT
Objective:
To investigate the mechanism responsible for homoharringtonine (HHT), which contributes to imatinib (IM) sensitivity in the chronic myeloid leukemia (CML) cell line.Methods:
We established cell lines from a patient with CML at the time of first diagnosis and relapse phase, and designated the cell lines as NPHA1 and NPHA2, respectively. Stable underexpressed EphB4 cells (NPHA2-EphB4-sh) were obtained. Leukemia cell lines were incubated with HHT. The activated signal proteins in cells were tested by Western blot.Results:
EphB4 was overexpressed in IM-resistant NPHA2 compared with the NPHA1 cell line. However, the expression of EphB4 mRNA and protein were significantly decreased in knockdown NPHA2-EphB4-sh cells compared with the NPHA2 and NPHA1 (P<0.001) cell lines. NPHA2-EphB4-sh cells were sensitive to IM (IC500.93 mg/L), and NPHA2 showed IM re-sistance (IC50 5.45 mg/L) (P<0.001). However, co-stimulation with HHT+IM decreased IC50 of NPHA2 cells to 1.17 mg/L (P<0.001). Meanwhile, phospho-Rac1/cdc42 was significantly increased in NPHA2 cells compared with NPHA2-EphB4-sh (P<0.001). HHT blocked the expression of EphB4/RhoA.Conclusion:
The overexpression of EphB4 contributed to IM resistance in CML line cells. EphB4/RhoA may be a new marker of IM resistance. HHT with IM yielded more treatment advantages than IM alone by blocking EphB4/RhoA pathways.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Tipo de estudo:
Estudo diagnóstico
Idioma:
Chinês
Revista:
Chinese Journal of Clinical Oncology
Ano de publicação:
2014
Tipo de documento:
Artigo
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