Sorafenib Induces Growth Inhibition and Apoptosis of Human Chondrosarcoma Cells by Blocking the RAF/ERK/MEK Pathway
Sorafenib Induces Growth Inhibition and Apoptosis of Human Chondrosarcoma Cells by Blocking the RAF/ERK/MEK Pathway
复制标题
索拉非尼通过阻断 RAF/ERK/MEK 通路诱导人软骨肉瘤细胞生长抑制和凋亡
DOI：
10.1002/jso.21661
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发表时间：
2010-12-01
影响因子：
2.5
通讯作者：
Zhao, Hui
中科院分区：
文献类型：
--
作者：
Lu, Xinchang;Tang, Xiaodong;Zhao, Hui
背景：软骨肉瘤是第二常见的原发恶性骨肿瘤，由于局部复发和有限的治疗选择而导致显著的发病率。传统的细胞毒性化疗已被证明对这种肉瘤基本无效。本文报道了索拉非尼对软骨肉瘤细胞系体外生长的抑制作用。方法：用索拉非尼处理软骨肉瘤细胞系(SW1353和CRL7891)。结果：索拉非尼能有效地抑制软骨肉瘤细胞的生长并诱导其凋亡，同时抑制磷酸化的MEK和磷酸化ERK的表达。细胞周期蛋白D1、Rb和抗凋亡蛋白Bclxl、Mcl-1的表达水平显著降低，而Bcl2、Bax的表达水平无明显变化。结论：索拉非尼对软骨肉瘤细胞株SW1353和CRL7891的RAS/Raf/MAPK通路具有时间和剂量依赖性抑制作用，提示索拉非尼可能成为软骨肉瘤患者治疗软骨肉瘤的新选择。J·奥科尔外科医生。2010；102：821-826。(C)2010年Wiley-Liss公司
Background: Chondrosarcoma represents the second most common primary malignant bone tumor causing significant morbidity due to local recurrence and limited treatment options. Conventional cytotoxic chemotherapy has been proven to be largely ineffective to this sarcoma. Here we report that sorafenib is effective in growth inhibition of chondrosarcoma cell lines in vitro.Methods: Chondrosarcoma cell lines (SW 1353 and CRL7891) were treated with sorafenib. Flow cytometry, DAPI assay, and Western blotting were employed to determine the effects of sorafenib in inhibitory proliferation and induce apoptosis in chondrosarcoma cells in vitro.Results: The results showed that sorafenib effectively inhibited cell growth and induced apoptosis in chondrosarcoma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Further more the expression levels of cyclin D1, Rb and anti-apoptotic proteins Bcl-xl and Mcl-1 significantly reduced, but no changes in Bcl-2 and Bax. We although detected the expression of Akt, JNK, p38 and their respective phosphoprotein, but did not found meaningful changes.Conclusions: Our findings demonstrate that sorafenib inhibited the Ras/Raf/MAPK pathway in a time-and dose-dependent fashion in chondrosarcoma cell lines SW 1353 and CRL7891 and suggest that sorafenib may be a new therapeutic option for patients with chondrosarcorna. J. Surg. Oncol. 2010;102:821-826. (C) 2010 Wiley-Liss, Inc.