Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity
Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity
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DOI：
10.1158/1078-0432.ccr-05-1335
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发表时间：
2005-12-15
影响因子：
11.5
通讯作者：
Sone, S
中科院分区：
文献类型：
--
作者：
Muguruma, H;Yano, SJ;Sone, S
目的：探讨新型抗生素逆转霉素A对人小细胞肺癌(SBC-5)细胞溶骨性骨转移的治疗作用。反转霉素A虽不能抑制SBC-5细胞的增殖，但能抑制甲状旁腺激素相关肽的表达。静脉接种自然杀伤细胞耗尽的严重联合免疫缺陷小鼠的SBC-5细胞，在包括骨骼在内的多个器官产生实验性转移。每日给予反转霉素A抑制骨转移，但不抑制内脏转移，呈剂量依赖关系。组织学分析显示，逆转霉素A虽然不影响肿瘤细胞的增殖数量，但却减少了破骨细胞的数量，增加了骨病变中的凋亡细胞。结论：逆转霉素A可能通过直接诱导细胞凋亡和间接抑制肿瘤细胞源性甲状旁腺激素相关肽的产生来抑制溶骨性骨转移。因此，反转霉素A可能是一种新的、有效的治疗肺癌骨转移的药物。
Purpose: The purpose of this study was to determine therapeutic effect of a novel antibiotic, reveromycin A, against osteolytic bone metastasis of human small cell lung cancer (SBC-5) cells.Results: Reveromycin A induced apoptosis specifically in osteoclasts in vitro. Although reveromycin A did not inhibit SBC-5 cell proliferation, it suppressed the expression of parathyroid hormone-related peptide. Intravenous inoculation of SBC-5 cells in natural killer cell-depleted severe combined immunodeficient mice produced experimental metastases in multiple organs, including the bone. Daily administration of reveromycin A inhibited the bone metastasis, but not visceral metastasis, in a dose-dependent manner. Histologic analyses revealed that although treatment with reveromycin A did not affect the number of proliferating tumor cells, it decreased the number of osteoclasts and increased apoptotic cells in bone lesions.Conclusions: These findings suggest that reveromycin A may inhibit osteolytic bone metastasis through suppression of osteoclast activity by directly inducing apoptosis and indirectly inhibiting tumor cell-derived parathyroid hormone-related peptide production. Therefore, reveromycin A may be a novel, potent therapeutic agent against osteolytic bone metastasis of lung cancer in humans.