Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2
Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2
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DOI：
10.1007/s00432-010-0938-0
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发表时间：
2011-05
影响因子：
3.6
通讯作者：
J. Kitagawa;T. Hara;H. Tsurumi;Soranobu Ninomiya;Kengo Ogawa;Seiji Adachi;N. Kanemura;S. Kasahara;M. Shimizu;H. Moriwaki
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文献类型：
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作者：
J. Kitagawa;T. Hara;H. Tsurumi;Soranobu Ninomiya;Kengo Ogawa;Seiji Adachi;N. Kanemura;S. Kasahara;M. Shimizu;H. Moriwaki
目的探讨非环维A酸类化合物(ACR)和维生素K2(VK2)对HL-60细胞的作用。用流式细胞仪检测细胞的Annexin V结合能力，以检测细胞的凋亡。为了评估细胞周期，我们使用了FITC BrdU Flow Kit和流式细胞仪。结果ACR和VK2呈剂量依赖性抑制HL-60细胞的增殖。这两种药物联合使用可协同抑制细胞生长并诱导细胞凋亡。VK2抑制Ras/MAPK信号通路的激活，ACR与VK2协同抑制RxRα的磷酸化，抑制HL-60细胞的生长。结论ACR和VK2对HL-60细胞具有协同作用，ACR和VK2联合作用可能为白血病的治疗提供新的策略。
PurposeThe aim of this study was to assess the effects of acyclic retinoid (ACR) and vitamin K2(VK2) in HL-60 cells.MethodsWe used HL-60 cells, and the Trypan Blue dye exclusion method was used for cell proliferation assays. For detection of apoptosis, the Annexin V–binding capacity of treated cells was examined by flow cytometry. To evaluate the cell cycle, we used a FITC BrdU Flow KIT and flow cytometry. Total extracted and equivalent amounts of protein were examined by Western blotting using specific antibodies.ResultsACR and VK2dose dependently inhibited the proliferation of HL-60 cells. These two agents in combination synergistically inhibited cell growth and induced apoptosis. VK2inhibited activation of the Ras/MAPK signaling pathway, and ACR plus VK2cooperatively inhibited phosphorylation of RXRα and the growth of HL-60 cells. Moreover, ACR and VK2induced increases in G0/G1 phase HL-60 cells, alone and synergistically in combination.ConclusionThe synergistic effects of ACR and VK2on HL-60 cells may provide a novel strategy for treating leukemia.