KMID : 1100120180250010023
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´ëÇÑ°ñ´ë»çÇÐȸÁö 2018 Volume.25 No. 1 p.23 ~ p.33
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¥á-Tocopheryl Succinate Inhibits Osteolytic Bone Metastasis of Breast Cancer by Suppressing Migration of Cancer Cells and Receptor Activator of Nuclear Factor-¥êB Ligand Expression of Osteoblasts
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Kim Bong-Jun
Kim Hong-Hee Lee Zang-Hee
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Abstract
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Background: Breast cancer is one of the most common cancers affecting women and has a high incidence of bone metastasis, causing osteolytic lesions. The elevated expression of receptor activator of nuclear factor-¥êB ligand (RANKL) in cancer activates osteoclasts, leading to bone destruction. We previously reported that ¥á-tocopheryl succinate (¥áTP-suc) inhibited interleukin-1-induced RANKL expression in osteoblasts. Here, we examined the effect of ¥áTP-suc on osteolytic bone metastasis in breast cancer.
Methods: To examine the effect of ¥áTP-suc on the metastatic capacity of breast cancer, MDA-MB-231-FL cells were injected into the left cardiac ventricle of BALB/c nude mice along with intraperitoneal injection of ¥áTP-suc. The mice were then analyzed by bioluminescence imaging. To investigate the effect of ¥áTP-suc on osteolysis, 4T1 cells were directly injected into the femur of BALB/c mice along with intraperitoneal injection of ¥áTP-suc. Microcomputed tomography analysis and histomorphometric analysis of the femora were performed.
Results: ¥áTP-suc inhibited cell migration and cell growth of 4T1 cells. In line with these results, bone metastasis of MDA-MB-231-FL cells was reduced in mice injected with ¥áTP-suc. In addition, ¥áTP-suc decreased osteoclastogenesis by inhibiting 4T1-induced RANKL expression in osteoblasts. Consistent with these results, 4T1-induced bone destruction was ameliorated by ¥áTP-suc, with in vivo analysis showing reduced tumor burden and osteoclast numbers.
Conclusions: Our findings suggest that ¥áTP-suc may be efficiently utilized to prevent and treat osteolytic bone metastasis of breast cancer with dual effects.
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KEYWORD
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Alpha-tocopheryl succinate, Breast neoplasms, Osteolysis
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