的二磷酸盐ibandronate促进细胞凋亡在人类乳腺癌mda - mb - 231细胞在骨转移。

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Hiraga T,威廉姆斯PJ,曼迪GR, Yoneda T

的二磷酸盐ibandronate促进细胞凋亡在人类乳腺癌mda - mb - 231细胞在骨转移。

癌症研究》2001年6月1日,61 (11):4418 - 24。

PubMed ID

11389070 (在PubMed

]

文摘

二磷酸盐(BP),破骨细胞的特定抑制剂,已被广泛用作有益剂治疗骨转移的乳腺癌患者。它非常认可,英国石油公司减少骨质溶解,促进破骨细胞凋亡。然而,最近的动物和人类的数据表明BPs不仅减少骨质溶解与转移性乳腺癌有关,但也减少骨骼的肿瘤负荷。后肿瘤负荷的机制却降低了英国石油公司管理是未知的。在这里,我们审查的影响在人类乳腺癌细胞mda - 231 BP ibandronate特征明显在骨转移动物模型骨转移。Ibandronate,管理(南卡罗来纳州日报;4 microg /鼠标/天)建立了骨转移后,抑制骨转移的发展建立了溶骨的影像学评估的分析。组织学和histomorphometrical检查显示ibandronate减少监测骨吸收,增加破骨细胞凋亡。此外,ibandronate也显著降低mda - 231肿瘤负荷,增加细胞凋亡在骨转移的乳腺癌细胞mda - 231。相比之下,ibandronate未能抑制mda - 231肿瘤形成没有影响在乳腺癌细胞mda - 231细胞凋亡原位乳腺脂肪垫。 These data suggest that the effects of ibandronate on apoptosis in MDA-231 breast cancer cells are restricted in bone in which ibandronate selectively deposits. Consistent with these in vivo results, a relatively high concentration of ibandronate (100 microM) increased caspase-3 activity and induced DNA fragmentation in MDA-231 breast cancer cells in culture. Moreover, a caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone, blocked ibandronate-induced DNA fragmentation in MDA-231 cells, suggesting an involvement of caspase-3 in ibandronate-induced apoptosis. Our results suggest that BP suppresses bone metastases through promotion of apoptosis in metastatic cancer cells as well as in osteoclasts. However, it still remains open whether BP has direct anticancer actions in vivo.

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药物

Ibandronate