Interference with actin dynamics is superior to disturbance of microtubule function in the inhibition of human ovarian cancer cell motility
Interference with actin dynamics is superior to disturbance of microtubule function in the inhibition of human ovarian cancer cell motility
复制标题
DOI：
10.1016/j.bcp.2008.06.014
复制
发表时间：
2008-09-15
影响因子：
5.8
通讯作者：
Boven, Epie
中科院分区：
文献类型：
--
作者：
Bijman, Marcel N. A.;van Berkel, Maria P. A.;Boven, Epie
细胞运动主要由肌动蛋白和微管细胞骨架协调，其中Rho GTP酶密切合作。我们研究了亚毒性和50%生长抑制浓度的细胞因子干扰剂是否会影响5种人卵巢癌细胞系的运动性。顺铂和多柔比星作为对照细胞毒性剂是无效的，微管靶向剂多西他赛，埃博霉素B和长春碱仅轻微抑制细胞运动，而肌动蛋白靶向剂细胞松弛素D是最有效的阻碍细胞迁移和侵袭。多西他赛对微管动力学的干扰对β-微管蛋白和F-肌动蛋白的细胞结构没有重要影响。与此相反，肌动蛋白动力学的细胞松弛素D的阻碍导致板状伪足延伸的损失，诱导厚层的F-肌动蛋白和细胞组织的紊乱。在OVCAR-3细胞中，多西他赛仅轻微降低Rac 1的活性，但细胞松弛素D明显降低Rac 1的活性。总之，靶向肌动蛋白细胞骨架可能提供一种防止转移形成的方法。(C)2008年爱思唯尔公司All rights reserved.
Cellular movement is mainly orchestrated by the actin and microtubule cytoskeleton in which Rho GTPases closely collaborate. We studied whether cytoskeleton-interfering agents at subtoxic and 50% growth-inhibiting concentrations affect motility of five unselected human ovarian cancer cell lines. Cisplatin and doxorubicin as control cytotoxic agents were not effective, the microtubule-targeting agents docetaxel, epothilone B and vinblastine only marginally inhibited cell motility, while the actin-targeting agent cytochalasin D was most potent in hampering both cell migration and invasion. Disturbance of microtubule dynamics by docetaxel did not importantly affect the cellular structures of beta-tubulin and F-actin. In contrast, hindrance of actin dynamics by cytochalasin D resulted in loss of lamellipodial extensions, induced thick layers of F-actin and disorder in cellular organization. In OVCAR-3 cells the activity of Rac1 was only slightly diminished by docetaxel, but clearly reduced by cytochalasin D. in conclusion, targeting the actin cytoskeleton might provide a means to prevent metastasis formation. (C) 2008 Elsevier Inc. All rights reserved.