机构地区:[1]The First Affiliated Hospital of Zhejiang Chinese Medical University [2]Institute of Hematology,the First Affiliated Hospital,College of Medicine,Zhejiang University
出 处:《Chinese Journal of Integrative Medicine》2015年第8期635-639,共5页中国结合医学杂志(英文版)
基 金:Supported by National Natural Science Foundation of China(No.30871099);Zhejiang Provincial Natural Science Foundation of China(No.R2090392);Administration of Traditional Chinese Medicine of Zhejiang Province(No.2000C25)
摘 要:Objective: To investigate whether CYC116 can potentiate matdne-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells. Methods: The dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an M'I-F assay and apoptosis induction was evaluated by flow cytometry. Activation ot the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting. Results: Matrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor K B (NF-κB). Conclusions: CYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.Objective: To investigate whether CYC116 can potentiate matdne-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells. Methods: The dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an M'I-F assay and apoptosis induction was evaluated by flow cytometry. Activation ot the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting. Results: Matrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor K B (NF-κB). Conclusions: CYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.
关 键 词:APOPTOSIS aurora kinase CYC116 INHIBITOR MATRINE multiple myeloma
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