Umbilical cord mesenchymal stem cells enhance imatinib-induced apoptosis in chronic myeloid leukemia
10.3969/j.issn.2095-4344.2017.25.016
- VernacularTitle:脐带间充质干细胞增强伊马替尼诱导慢性粒细胞白血病细胞的凋亡
- Author:
Ying LIU
;
Baoquan SONG
;
Yimeng WEI
;
Huifang FAN
;
Yi YU
;
Shuxu DONG
;
Zhongchao HAN
;
Fengxia MA
- From:
Chinese Journal of Tissue Engineering Research
2017;21(25):4032-4037
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Imatinib has a significant pro-apoptosis effect on chronic myelogenous leukemia (CML), but there are still some patients being resistant to it. Human umbilical cord mesenchymal stem cells (hUC-MSCs) affect the apoptosis of a variety of hematologic malignancies. However, the impacts of hUC-MSCs on the apoptosis of CML cells induced by imatinib remain unclear.OBJECTIVE: To investigate whether hUC-MSCs have an influence on the apoptosis of K562 cells induced by imatinib and to reveal the possible underlying mechanism.METHODS: K562 cells were cultured with hUC-MSCs or/and imatinib. Cellular apoptosis was measured with Annexin-V and PI staining by flow cytometry analysis. The protein expressions of Bax, Bcl-2, caspase-3, caspase-9 and cleaved-PARP in K562 cells were detected by western blot assay. Pan-caspase inhibitor Z-VAD-FMK was used to block apoptosis in each group, and during this process the effect of caspase apoptosis signaling pathway was detected.RESULTS AND CONCLUSION: The apoptosis of K562 cells was enhanced, when imatinib was combined with hUC-MSCs. Western blot analysis showed that the expression of pro-apoptotic protein Bax was enhenced and the expression of anti-apoptotic protein Bcl-2 was suppressed. Furthermore, the cleaved forms of caspase-9, caspase-3 and PARP in K562 cell were higher in the hUC-MSCs+imatinib group than in the imatinib group. The apoptosis of K562 cells induced by the hUC-MSCs combined with imatinib was significantly inhibited by Z-VAD-FMK. In conclusion, these findings indicate that hUC-MSCs can enhance imatinib-induced apoptosis of K562 cells by activating caspase apoptosis signaling pathway.
