Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway.
Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway.
复制标题
金丝桃素通过 NFATc1 信号通路靶向破骨细胞并预防乳腺癌诱导的骨转移
DOI：
10.18632/oncotarget.22930
复制
发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Ouyang Z;Guo X;Chen X;Liu B;Zhang Q;Yin Z;Zhai Z;Qu X;Liu X;Peng D;Shen Y;Liu T;Zhang Q
骨是乳腺癌最常见的转移靶器官。由于与尿道相关的事件，这产生了相当大的发病率，并严重降低了生活质量。破骨细胞活性增加与骨微环境中的乳腺癌生长有关。我们先前观察到金丝桃素（一种天然植物化合物）具有抗骨质疏松活性，这使我们研究金丝桃素是否可以抑制乳腺癌引起的骨转移和骨质溶解。我们发现金丝桃素抑制乳腺癌细胞刺激的破骨细胞的上调。金丝桃素对破骨细胞和乳腺癌介导的破骨细胞生成的活性与抑制NFATc 1信号通路和减弱Ca 2+振荡有关。此外，金丝桃素抑制乳腺癌细胞的侵袭和迁移，但对乳腺癌细胞诱导的成骨细胞RANKL/OPG比值或破骨细胞活化因子的表达几乎没有影响。金丝桃素的管理可以减少肿瘤负荷，骨溶解诱导的MDA-MB-231细胞直接接种到胫骨骨髓腔，以及骨转移，并提高生存率的实验转移模型，通过心内注射MDA-MB-231乳腺癌细胞。综上所述，这些结果表明金丝桃素可能是一种潜在的天然药物，用于预防和治疗乳腺癌骨转移患者的骨破坏。
Bone is the most common target organ of metastasis of breast cancers. This produces considerable morbidity due to skeletal-related events, and severely reduces the quality of life. Increased osteoclast activity is implicated in breast cancer outgrowth in the bone microenvironment. Our previous observation of an anti-osteoclastic activity of hypericin, a natural plant compound, led us to investigate whether hypericin could inhibit bone metastasis and osteolysis caused by breast cancer. We find that hypericin inhibited the upregulation of osteoclasts stimulated by breast cancer cells. The activity of hypericin on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of NFATc1 signaling pathway and attenuation of Ca2+ oscillation. Furthermore, hypericin suppresses invasion and migration in breast cancer cells, but has little effect on breast cancer-cell induced RANKL/OPG ratio in osteoblast or the expression of osteoclast-activating factors. Administration of hypericin could reduce tumor burden, osteolysis induced by direct inoculation of MDA-MB-231 cells into the bone marrow cavity of the tibia as well as metastasis of bone and improve survival in an experimental metastasis model by intracardiac injection of MDA-MB-231 breast cancer cells. Taken together, these results suggest that hypericin may be a potential natural agent for preventing and treating bone destruction in patients with bone metastasis due to breast cancer.
登录
查看更多内容
影响因子：
4
作者：
Casimiro, Sandra;Luis, Ines;Costa, Luis
通讯作者：
Costa, Luis
影响因子：
28.4
作者：
Hortobagyi, Gabriel N.;Van Poznak, Catherine;Lipton, Allan
通讯作者：
Lipton, Allan
DOI：
10.1186/bcr2781
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Chen YC;Sosnoski DM;Mastro AM
通讯作者：
Mastro AM
破骨细胞 miR-214 靶向 TRAF3，促进乳腺癌的溶骨性骨转移。
影响因子：
4.6
作者：
Liu J;Li D;Dang L;Liang C;Guo B;Lu C;He X;Cheung HY;He B;Liu B;Li F;Lu J;Wang L;Shaikh AB;Jiang F;Lu C;Peng S;Zhang Z;Zhang BT;Pan X;Xiao L;Lu A;Zhang G
通讯作者：
Zhang G
影响因子：
3.7
作者：
Kurio, Naito;Shimo, Tsuyoshi;Sasaki, Akira
通讯作者：
Sasaki, Akira