掺铁的 45S5 生物活性玻璃成分会损害体外转移性人类乳腺癌细胞的代谢活性和增殖。

Nina Hildenbrand, Wilko Thiele, Elena Tripel, Tobias Renkawitz, Farzad Kermani, Ahmed El-Fiqi, Fabian Westhauser
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摘要

包括乳腺癌在内的多种人类肿瘤经常转移至骨骼,容易造成病理性骨折。骨转移瘤的手术治疗包括切除转移瘤和骨修复。目前修复骨缺损的手术方法包括使用聚甲基丙烯酸甲酯(PMMA)骨水泥。生物活性玻璃(BG)微粒是一种很有前途的替代材料,它不仅具有物理稳定性,还能诱导骨再生。此外,掺杂 Fe2O3 的 BG 还可能对肿瘤细胞产生负面影响。在此,我们测试了 BGs 可影响转移性人类乳腺癌细胞的假设。为此,我们在体外评估了含或不含 Fe2O3 的不同 BG 成分对转移性人 MDA-MB-231 乳腺癌细胞的影响。我们发现,所有测试的 BG 都会以浓度依赖性的方式损害乳腺癌细胞的活力和增殖。抗增殖作用与 BG 颗粒大小成反比,在作为对照的间充质基质细胞(MSCs)中的抗增殖作用一般不明显。此外,与不含 Fe2O3 的 BG 相比,掺有 Fe2O3 的 BG 对肿瘤细胞增殖和代谢活动的抑制作用更强。因此,我们的数据表明,BGs 对人类乳腺癌细胞的影响比间叶干细胞更强,并表明 Fe2O3 的存在可增强 BGs 的抗增殖和抗代谢作用。因此,掺杂 Fe2O3 的 BGs 有可能被用于转移性骨病变的外科治疗,而且除了再生特性外,还能对骨转移进行局部控制。
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Fe-doped 45S5 bioactive glass compositions impair the metabolic activity and proliferation of metastatic human breast cancer cellsin vitro.

Many kinds of human tumors, including breast carcinomas, frequently metastasize to the bone, making it prone to pathologic fractures. Surgical management of bone metastases ranges from the resection of metastases to bone repair. Current surgical methods for the repair of bone defects include the use of polymethyl methacrylate (PMMA)-based bone cements. A promising alternative material are bioactive glass (BG) particles that in addition to providing physical stability can also induce bone regeneration. Moreover, BGs doped with Fe2O3may also have a negative impact on tumor cells. Here, we tested the hypothesis that BGs can affect metastatic human breast cancer cells. To this end, we assessed the effects of different BG compositions with and without Fe2O3on metastatic human MDA-MB-231 breast cancer cellsin vitro. We found that all BGs tested impaired the viability and proliferation of breast cancer cells in a concentration-dependent manner. The anti-proliferative effects inversely correlated with BG particle size, and were in general less pronounced in mesenchymal stromal cells (MSCs) that served as a control. Moreover, Fe2O3-doped BGs were more potent inhibitors of tumor cell proliferation and metabolic activity than Fe2O3-free BG. Our data therefore indicate that BGs can affect human breast cancer cells more strongly than MSCs, and suggest that the presence of Fe2O3can potentiate anti-proliferative and anti-metabolic effects of BGs. Fe2O3-doped BGs thus have the potential to be used for the surgical management of metastatic bone lesions, and may in addition to their regenerative properties also allow the local control of bone metastases.

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