Oda Miki, Iwaya Keiichi, Kikuchi Ryoko, Kobayashi Takayuki, Yoneda Toshiyuki, Nishikawa Kahoko, Matsubara Osamu, Kohno Norio
Department of Breast Oncology, Tokyo Medical University, Shinjuku, Tokyo, Japan; Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
J Bone Oncol. 2012 Jul 18;1(2):40-6. doi: 10.1016/j.jbo.2012.06.001. eCollection 2012 Sep.
Zoledronic acid (Zol) is the most potent inhibitor of bone resorption among the bisphosphonates and is commonly used for inhibiting bone metastasis. However, it remains unclear whether Zol provides a survival benefit. Recent findings indicate that epidermal growth factor (EGF) signaling is an important mediator of bone metastasis. Thus, we examined the combined effects of Zol and an EGF receptor-tyrosine kinase inhibitor, gefitinib, on the proliferation and invasion of a bone-seeking clone and the breast cancer cell line MDA-MB-231. Combined treatment with Zol and gefitinib synergistically inhibited both invasion and cell proliferation of the bone-seeking clone, but not those of the MDA-MB-231 cells. Two-dimensional difference gel electrophoresis and mass spectrometry demonstrated that stathmin was down-regulated during these cooperative effects. Stathmin is a signal transduction regulatory factor which plays an important role in cell division and malignant tumor development. Our data suggest that stathmin may be a promising target molecule for blocking bone metastasis of breast cancer.
唑来膦酸（Zol）是双膦酸盐类中抑制骨吸收作用最强的药物，常用于抑制骨转移。然而，Zol是否能带来生存获益仍不明确。最近的研究结果表明，表皮生长因子（EGF）信号传导是骨转移的重要介质。因此，我们研究了Zol与一种表皮生长因子受体酪氨酸激酶抑制剂吉非替尼联合使用对亲骨克隆和乳腺癌细胞系MDA-MB-231增殖及侵袭的影响。Zol与吉非替尼联合治疗可协同抑制亲骨克隆的侵袭和细胞增殖，但对MDA-MB-231细胞无此作用。二维差异凝胶电泳和质谱分析表明，在这些协同作用过程中，微管相关蛋白2（stathmin）表达下调。Stathmin是一种信号转导调节因子，在细胞分裂和恶性肿瘤发展中起重要作用。我们的数据表明，stathmin可能是阻断乳腺癌骨转移的一个有前景的靶分子。
