Differentiation induction of human breast cancer cells by arsenite in combination with tetrandrine.
Differentiation induction of human breast cancer cells by arsenite in combination with tetrandrine.
复制标题
亚砷酸盐与粉防己碱联合诱导人乳腺癌细胞分化。
DOI：
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发表时间：
2020-02
影响因子：
2.2
通讯作者：
Takagi Norio
中科院分区：
文献类型：
--
作者：
Yu Bowen;Yuan Bo;Kiyomi Anna;Kikuchi Hidetomo;Hayashi Hideki;Hu Xiaomei;Okazaki Mari;Sugiura Munetoshi;Hirano Toshihiko;Pei Xiaohua;Takagi Norio
背景
为了提供新的洞察力的发展，新的治疗策略，以打击乳腺癌，分化诱导活性的临床可达到的浓度的亚砷酸盐（AsIII）和粉防己碱（Tetra）在乳腺癌细胞系MDA-MB-231和MCF-7进行了研究。
方法
流式细胞仪分析癌细胞的分化诱导。分别用Western印迹法和细胞活力测定法分析人正常外周血单个核细胞（PBMC）分化和增殖相关基因的改变。
结果
暴露于单独的Tetra或与AsIII组合诱导两种细胞的分化，其特征在于ICAM-1的上调，Her 2/neu的下调。与MCF-7相比，低浓度的AsIII和Tetra的组合诱导MDA-MB-231的分化，表明MDA-MB-231细胞对分化高度敏感。这种分化与Erk信号通路的激活平行发生，并被一种有效的Erk抑制剂PD 98059所消除。与体外实验结果一致，在我们先前研究获得的异种移植小鼠中的MDA-MB-231乳腺肿瘤中也观察到ICAM-1的上调和Erk信号通路的激活。在能够诱导MDA-MB-231细胞分化的浓度下，AsIII与Tetra联合暴露后，未观察到明显的PBMC增殖抑制。
结论
Erk信号通路可能在乳腺癌细胞体内外分化诱导中起重要作用。总的来说，我们的研究结果表明，该组合可能成为开发不同类型乳腺癌新治疗方法的有希望的候选药物。
BACKGROUND
To provide novel insight into the development of new therapeutic strategies to combat breast cancer, differentiation-inducing activity of clinically achievable concentrations of arsenite (AsIII) and tetrandrine (Tetra) was investigated in breast cancer cell lines MDA-MB-231 and MCF-7.
METHODS
Differentiation induction of cancer cells was analyzed by flow cytometer. Alterations of genes related to differentiation, and proliferation of human normal peripheral blood mononuclear cells (PBMCs) were analyzed using western blotting and cell viability assay, respectively.
RESULTS
Exposure to Tetra alone or in combination with AsIII induced differentiation of both cells characterized by upregulation of ICAM-1, downregulation of Her2/neu. In comparison with MCF-7, the combination of lower concentrations of AsIII and Tetra induced differentiation of MDA-MB-231, indicating that MDA-MB-231 cells were highly susceptible to differentiation. The differentiation occurred in parallel with activation of Erk signaling pathway, and was abolished by PD98059, a potent Erk inhibitor. Consistent with in vitro experimental results, the upregulation of ICAM-1 and the activation of Erk signaling pathway were also observed in MDA-MB-231 breast tumors in xenograft mouse obtained from our previous study. No obvious proliferation inhibition of PBMCs was observed following the exposure to AsIII combined with Tetra at the concentrations capable of inducing differentiation of MDA-MB-231 cells.
CONCLUSION
The Erk signaling pathway may be crucially involved in the differentiation induction of breast cancer cells in vitro and in vivo. Collectively, our results suggest that the combination can probably serve as promising candidates for the development of novel therapeutic approaches for different types of breast cancer.
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影响因子：
4.2
作者：
Zhao Y;Onda K;Sugiyama K;Yuan B;Tanaka S;Takagi N;Hirano T
通讯作者：
Hirano T
DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
影响因子：
3.8
作者：
Baj, G;Arnulfo, A;Ferrero, E
通讯作者：
Ferrero, E
影响因子：
4.6
作者：
BACUS, SS;KIGUCHI, K;HUBERMAN, E
通讯作者：
HUBERMAN, E
影响因子：
5.8
作者：
Yuan B;Yao M;Wang X;Sato A;Okazaki A;Komuro H;Hayashi H;Toyoda H;Pei X;Hu X;Hirano T;Takagi N
通讯作者：
Takagi N