Artemisinin inhibits breast cancer-induced osteolysis by inhibiting osteoclast formation and breast cancer cell proliferation
Artemisinin inhibits breast cancer-induced osteolysis by inhibiting osteoclast formation and breast cancer cell proliferation
复制标题
青蒿素通过抑制破骨细胞形成和乳腺癌细胞增殖来抑制乳腺癌引起的骨溶解
DOI：
10.1002/jcp.27875
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Yao, Jun
中科院分区：
文献类型：
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作者：
Li, Jia;Feng, Wenyu;Yao, Jun
青蒿素(Art)除了用于治疗疟疾外，还可用作抗炎和抗肿瘤药物。在这项研究中，我们评估了ART对破骨细胞的形成和激活以及对骨中乳腺癌细胞发展的影响。为了评价阿糖胞苷对破骨细胞体外分化的影响，我们用不同浓度的阿糖胞苷处理骨髓来源的巨噬细胞，并检测了参与破骨细胞形成的基因和蛋白的表达。我们还进行了细胞计数Kit-8实验，以评估Art对BMMS和MDA-MB-231细胞的毒性。我们还进行了Transwell实验、伤口愈合实验、集落形成实验和细胞凋亡实验，以评估Art对MDA-MB-231细胞的影响。我们还使用裸鼠模型评估了ART在体内破骨细胞骨吸收实验中的作用。我们证明，即使ART对破骨细胞无毒，它也能抑制破骨细胞的分化和建立。此外，ART以浓度依赖的方式减少破骨细胞形成相关基因的表达，并抑制破骨细胞的骨吸收。根据我们的研究结果，我们认为Art通过激活细胞凋亡途径抑制乳腺癌细胞的增殖，并通过抑制组织蛋白酶K、ATPase H+转运V0亚单位D2、活化的T细胞核因子1、降钙素受体和抗酒石酸酸性磷酸酶的激活以及抑制核因子-B的激活来抑制破骨细胞的形成和分化。
In addition to being used to treat malaria, artemisinin (Art) can be used as an anti-inflammatory and antitumor agent. In this study, we evaluated the effects of Art on osteoclast formation and activation and on the development of breast cancer cells in bone. To evaluate the effect of Art on osteoclast differentiation in vitro, we treated bone marrow-derived macrophages (BMMs) with various concentrations of Art and evaluated the expression of genes and proteins involved in osteoclast formation. We also performed cell counting kit-8 assays to evaluate the toxicity of Art in BMMs and MDA-MB-231 cells. We also performed Transwell assays, wound-healing assays, colony formation assays, and cell apoptosis assays to evaluate the effect of Art in MDA-MB-231 cells. We also evaluated the effect of Art in an in vivo osteoclast bone resorption assay using a nude mouse model. We demonstrated that Art inhibits the differentiation and establishment of osteoclasts even though Art is not toxic to osteoclasts. In addition, Art reduced expression of genes involved in osteoclast formation and inhibited osteoclast bone resorption in a concentration-dependent manner. Based on our data, we believe that Art can inhibit proliferation of breast cancer cells by activating apoptosis pathways, and inhibit osteoclast formation and differentiation by inhibiting activation of cathepsin K, ATPase H+ transporting V0 subunit D2, nuclear factor of activated T cells 1, calcitonin receptor, and tartrate-resistant acid phosphatase and by inhibiting nuclear factor-B activation.