Nitrosative stress in rotated three-dimensional colorectal carcinoma cell cultures induces microtubule depolymerization and apoptosis.
Nitrosative stress in rotated three-dimensional colorectal carcinoma cell cultures induces microtubule depolymerization and apoptosis.
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DOI：
10.1158/0008-5472.can-03-3663
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发表时间：
2004-04
期刊：
影响因子：
11.2
通讯作者：
L. Laguinge;Shuling Lin;R. Samara;A. Salesiotis;J. Jessup
中科院分区：
文献类型：
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作者：
L. Laguinge;Shuling Lin;R. Samara;A. Salesiotis;J. Jessup
恶性细胞在转移到转移部位的过程中遇到流体剪切应力时发生失巢凋亡。我们假设，细胞内一氧化氮（NO）有助于这种细胞死亡，通过比较人结直肠癌细胞在低流体剪切应力旋转三维（旋转3-D）培养物中的生长与静态三维（静态3-D）非粘附表面上的培养物和二维单层（单层2-D）培养物中的生长。NO，微管的损失，和细胞凋亡显着增加，在旋转的3-D文化在10分钟内，并持续在24小时，而抑制NO合酶减少细胞凋亡和细胞内NO和防止微管蛋白降解。因此，流体剪切应力和三维生长增加NO合酶和NO，导致微管蛋白分解并诱导失巢凋亡。进入循环的恶性肿瘤细胞内的NO可能是大肠癌转移的一个新靶点。
Malignant cells undergo anoikis as they encounter fluid shear stress during transit to a metastatic site. We postulated that intracellular nitric oxide (NO) contributes to this cell death by comparing the growth of human colorectal carcinoma cells in low fluid shear stress rotated three-dimensional (Rotated 3-D) cultures with growth in static three-dimensional (Static 3-D) cultures on nonadherent surfaces and with two-dimensional monolayer (Monolayer 2-D) cultures. NO, loss of microtubules, and apoptosis increased significantly in Rotated 3-D cultures within 10 min and persisted at 24 h, whereas inhibition of NO synthase decreased apoptosis and intracellular NO and prevented tubulin degradation. Thus, fluid shear stress and three-dimensional growth increases NO synthase and NO to cause tubulin breakdown and induce anoikis. Intracellular NO in malignant cells entering the circulation may be a novel target for metastasis by colorectal carcinoma.