Susa Michiro, Morii Takeshi, Yabe Hiroo, Horiuchi Keisuke, Toyama Yoshiaki, Weissbach Lawrence, Hornicek Francis J, Morioka Hideo
Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
Anticancer Res. 2009 Jun;29(6):1879-88.
Conventional chemotherapy is ineffective for high-grade chondrosarcomas, highlighting the need for improved chemotherapies. Various clinical trials have been initiated using antiapoptotic agents and perifosine, and are truly in the experimental phases. Chondrosarcoma is still therefore considered a surgical disease despite its aggressive features of recurring locally and spreading to the lungs. Bisphosphonates inhibit growth of various cell types, including cancer cells and perhaps chondrosarcoma.
The effect of different concentrations of alendronate on cell proliferation, migration, apoptosis and cytoskeleton reorganization as well as on the regulation of intracellular protein expression were analyzed for the high-grade chondrosarcoma cell line CS-1. Mevalonate pathway intermediates were used in some experiments to assess mechanistic aspects.
Alendronate decreased cell viability of CS-1 by inhibiting cell proliferation and cell migration. Alendronate-induced loss of cell viability led to a sequence of events including apoptosis and cytoskeletal rearrangements. Moreover, changes in the expression levels of various proteins involved in cell proliferation, migration, cell cycle, apoptosis and cytoskeleton reorganization were demonstrated.
Alendronate exerts antiproliferative effects by perturbing various signaling pathways in CS-1 cells. These findings may lead to new treatment options for high-grade chondrosarcoma.
传统化疗对高级别软骨肉瘤无效，这凸显了改进化疗方法的必要性。目前已开展了多项使用抗凋亡药物和哌立福新的临床试验，且这些试验仍处于真正的实验阶段。因此，尽管软骨肉瘤具有局部复发和肺转移的侵袭性特征，但它仍被视为一种外科疾病。双膦酸盐可抑制包括癌细胞以及可能的软骨肉瘤细胞在内的多种细胞类型的生长。
分析了不同浓度阿仑膦酸钠对高级别软骨肉瘤细胞系CS-1的细胞增殖、迁移、凋亡、细胞骨架重组以及细胞内蛋白表达调控的影响。在一些实验中使用甲羟戊酸途径中间体来评估作用机制方面。
阿仑膦酸钠通过抑制细胞增殖和细胞迁移降低了CS-1的细胞活力。阿仑膦酸钠诱导的细胞活力丧失引发了一系列事件，包括凋亡和细胞骨架重排。此外，还证明了参与细胞增殖、迁移、细胞周期、凋亡和细胞骨架重组的各种蛋白质表达水平的变化。
阿仑膦酸钠通过干扰CS-1细胞中的各种信号通路发挥抗增殖作用。这些发现可能为高级别软骨肉瘤带来新的治疗选择。
