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全身振动对小鼠乳腺癌骨转移和血管生成的影响。

Effects of Whole-Body Vibration on Breast Cancer Bone Metastasis and Vascularization in Mice.

机构信息

Biomedical Engineering Laboratory, Tokushima University Graduate School of Technology, Industrial and Social Sciences, 770-8506, Tokushima, Japan.

Biomedical Engineering Laboratory, Tokushima University Faculty of Science and Technology, 770-8506, Tokushima, Japan.

出版信息

Calcif Tissue Int. 2022 Nov;111(5):535-545. doi: 10.1007/s00223-022-01009-4. Epub 2022 Jul 27.

DOI:10.1007/s00223-022-01009-4
PMID:35896728
Abstract

We evaluated whether whole-body vibration (WBV) prevented bone loss induced by breast cancer (BC) metastasis and the involvement of bone marrow vasculature. One day after orthotopic transplantation of mammary 4T1 tumor cells, 8-week-old BALB/c mice were subjected to 0.3 g/90 Hz vertical vibration for 20 min/day for 5 days/week (BC-WBV) or sham-handled (BC-Sham) over 3 weeks. Age-matched intact mice (Intact) were also sham-handled. Both tibiae were harvested from BC-WBV (n = 7), BC-Sham (n = 9), and Intact (n = 5) mice for bone structure imaging by synchrotron radiation-based computed tomography (SRCT) and hematoxylin and eosin staining, whereas right tibiae were harvested from other BC-WBV and BC-Sham (n = 6 each) mice for vascular imaging by SRCT. Tumor cells were similarly widespread in the marrow in BC-WBV and BC-Sham mice. In BC-Sham mice, cortical bone volume, trabecular volume fraction, trabecular thickness, trabecular number density, and bone mineral density were smaller, and marrow volume and trabecular separation were larger than in Intact mice. However, although trabecular thickness was smaller in BC-WBV than Intact mice, the others did not differ between the two groups. Serum osteocalcin tended to be higher in BC-WBV than BC-Sham mice. Compared with BC-Sham mice, BC-WBV mice had a smaller vessel diameter, a trend of a larger vessel number density, and smaller vessel diameter heterogeneity. In conclusion, WBV mitigates bone loss in BC bone metastasis, which may be partly due to increased bone anabolism. The alteration of marrow vasculature appears to be favorable for anti-tumor drug delivery. Further studies are needed to clarify the multiple actions of WBV on bone, tumor, and marrow vasculature and how they contribute to bone protection in BC metastasis.

摘要

我们评估了全身振动(WBV)是否可以预防乳腺癌(BC)转移引起的骨质流失和骨髓血管的参与。在乳腺 4T1 肿瘤细胞原位移植后 1 天,将 8 周龄 BALB/c 小鼠接受 0.3 g/90 Hz 垂直振动,每天 20 分钟,每周 5 天(BC-WBV)或假处理(BC-Sham),共 3 周。年龄匹配的完整小鼠(Intact)也进行假处理。从 BC-WBV(n=7)、BC-Sham(n=9)和 Intact(n=5)小鼠中采集双侧胫骨,通过同步辐射计算机断层扫描(SRCT)和苏木精和伊红染色进行骨结构成像,而从其他 BC-WBV 和 BC-Sham 小鼠(n=6 只)中采集右侧胫骨,通过 SRCT 进行血管成像。肿瘤细胞在 BC-WBV 和 BC-Sham 小鼠的骨髓中同样广泛分布。在 BC-Sham 小鼠中,皮质骨体积、小梁体积分数、小梁厚度、小梁数量密度和骨矿物质密度较小,骨髓体积和小梁分离较大。然而,尽管 BC-WBV 小鼠的小梁厚度比 Intact 小鼠小,但两组之间没有差异。BC-WBV 小鼠的血清骨钙素水平趋于高于 BC-Sham 小鼠。与 BC-Sham 小鼠相比,BC-WBV 小鼠的血管直径较小,血管数量密度趋势较大,血管直径异质性较小。总之,WBV 减轻了 BC 骨转移中的骨质流失,这可能部分是由于骨合成代谢增加。骨髓血管的改变似乎有利于抗肿瘤药物的输送。需要进一步的研究来阐明 WBV 对骨骼、肿瘤和骨髓血管的多种作用以及它们如何有助于 BC 转移中的骨骼保护。

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