Homoharringtonine contributes to imatinib sensitivity in chronic myeloid leukemia cell lines
10.3969/j.issn.1000-8179.20140758
- VernacularTitle:高三尖杉酯碱增强慢性粒细胞白血病细胞对于伊马替尼敏感性的研究
- Author:
Bintao HUANG
;
Weihong ZHAO
;
Zhen XIAO
;
Da GAO
- Publication Type:Journal Article
- Keywords:
homoharringtonine;
imatinib;
chronic myeloid leukemia
- From:
Chinese Journal of Clinical Oncology
2014;(16):1017-1020
- CountryChina
- Language:Chinese
-
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 (IC50:0.93 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.
