Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts.
Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts.
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DOI：
10.1038/srep19074
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发表时间：
2016-01-08
影响因子：
4.6
通讯作者：
Hong D
中科院分区：
文献类型：
--
作者：
Feng MX;Hong JX;Wang Q;Fan YY;Yuan CT;Lei XH;Zhu M;Qin A;Chen HX;Hong D
骨是乳腺癌最常见的远处复发部位，导致严重的并发症，严重影响患者的生活质量。据信，转移性乳腺癌细胞和破骨细胞之间的串扰是乳腺癌诱导的骨质溶解的关键。在这项研究中，双氢青蒿素（DHA）对破骨细胞的形成，骨吸收，成骨细胞分化和矿化的影响进行了初步评估，在体外，然后在体内钛颗粒诱导的骨溶解模型进行了进一步的调查。基于DHA对骨溶解的抑制作用，本研究进一步将DHA应用于MDA-MB-231乳腺癌诱导的小鼠骨溶解模型，并进一步探讨其分子机制。在这里，我们首次证实了DHA通过抑制AKT/SRC途径抑制破骨细胞分化、F-肌动蛋白环形成和骨吸收，从而导致DHA对钛颗粒诱导的骨溶解的预防作用，而不影响成骨细胞功能。更重要的是，我们证明DHA通过调节AKT信号通路抑制MDA-MB-231细胞的增殖、迁移和侵袭来抑制乳腺肿瘤诱导的骨质溶解。总之，DHA有效地抑制破骨细胞生成，防止乳腺癌引起的骨质溶解。
Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients’ quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.