Curcumin analogue UBS109 prevents bone loss in breast cancer bone metastasis mouse model: involvement in osteoblastogenesis and osteoclastogenesis.
Curcumin analogue UBS109 prevents bone loss in breast cancer bone metastasis mouse model: involvement in osteoblastogenesis and osteoclastogenesis.
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姜黄素类似物 UBS109 可预防乳腺癌骨转移小鼠模型中的骨质流失：参与成骨细胞生成和破骨细胞生成。
DOI：
10.1007/s00441-014-1846-4
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发表时间：
2014
影响因子：
3.6
通讯作者：
Shoji,Mamoru
中科院分区：
文献类型：
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作者：
Yamaguchi,Masayoshi;Zhu,Shijun;Zhang,Shumin;Wu,Daqing;Moore,TerryM;Snyder,JamesP;Shoji,Mamoru
乳腺癌的骨转移通常会导致骨溶解，从而导致严重的病理性骨折和高钙血症。骨稳态是通过成骨细胞和破骨细胞巧妙地调节的。乳腺癌骨转移的骨质流失可能是由于破骨细胞骨吸收的激活和成骨细胞骨形成的抑制。本研究旨在确定新型姜黄素类似物UBS109是否对乳腺癌细胞骨转移引起的骨质流失具有预防作用。裸鼠左右胫骨头部分别接种乳腺癌MDA-MB-231骨转移细胞（106个/只）。接种1周后，小鼠分别接受对照组（对照）、口服（p.o） UBS109（50或150 mg/kg体重）或腹腔注射（i.p） UBS109（10或20 mg/kg体重），每天1次，每周5天，连续7周。UBS109给药7周后，后肢采用x线诊断系统和苏木精染色和侵蚀染色评估溶骨破坏。从股骨和胫骨获得的骨髓细胞进行体外和体外培养，以评估成骨细胞矿化和破骨细胞发生。在接种乳腺癌MDA-MB-231骨转移细胞的小鼠胫骨中发现了显著的骨质流失。体内口服UBS109（50和150 mg/kg体重）和口服UBS109（10和20 mg/kg）可预防骨质流失。从乳腺癌细胞骨转移小鼠的骨组织中获得的骨髓细胞体外培养显示出抑制成骨细胞矿化和刺激破骨细胞发生的作用。这些变化在用UBS109处理的小鼠骨髓细胞培养后未见。此外，在体外正常裸鼠骨髓细胞中发现UBS109可刺激成骨细胞矿化并抑制脂多糖诱导的破骨细胞生成。这些发现表明，新的姜黄素类似物UBS109通过刺激成骨细胞矿化和抑制破骨细胞生成来预防乳腺癌细胞骨转移引起的骨质流失。
Bone metastasis of breast cancer typically leads to osteolysis, which causes severe pathological bone fractures and hypercalcemia. Bone homeostasis is skillfully regulated through osteoblasts and osteoclasts. Bone loss with bone metastasis of breast cancer may be due to both activation of osteoclastic bone resorption and suppression of osteoblastic bone formation. This study was undertaken to determine whether the novel curcumin analogue UBS109 has preventive effects on bone loss induced by breast cancer cell bone metastasis. Nude mice were inoculated with breast cancer MDA-MB-231 bone metastatic cells (106cells/mouse) into the head of the right and left tibia. One week after inoculation, the mice were treated with control (vehicle), oral administration (p.o.) of UBS109 (50 or 150 mg/kg body weight), or intraperitoneal administration (i.p.) of UBS109 (10 or 20 mg/kg body weight) once daily for 5 days per week for 7 weeks. After UBS109 administration for 7 weeks, hind limbs were assessed using an X-ray diagnosis system and hematoxylin and eosion staining to determine osteolytic destruction. Bone marrow cells obtained from the femurs and tibias were cultured to estimate osteoblastic mineralization and osteoclastogenesis ex vivo and in vitro. Remarkable bone loss was demonstrated in the tibias of mice inoculated with breast cancer MDA-MB-231 bone metastatic cells. This bone loss was prevented by p.o. administration of UBS109 (50 and 150 mg/kg body weight) and i.p. treatment of UBS109 (10 and 20 mg/kg) in vivo. Culture of bone marrow cells obtained from the bone tissues of mice with breast cancer cell bone metastasis showed suppressed osteoblastic mineralization and stimulated osteoclastogenesis ex vivo. These changes were not seen after culture of the bone marrow cells obtained from mice treated with UBS109. Moreover, UBS109 was found to stimulate osteoblastic mineralization and suppress lipopolysaccharide (LPS)-induced osteoclastogenesis in bone marrow cells obtained from normal nude mice in vitro. These findings suggest that the novel curcumin analogue UBS109 prevents breast cancer cell bone metastasis-induced bone loss by stimulating osteoblastic mineralization and suppressing osteoclastogenesis.