Abstract：
Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor-eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.
摘要：
结直肠癌（CRC）以其高死亡率和高转移特征而著称。血流产生的剪切力提供了调节细胞多种反应的机械信号，包括转移性癌细胞，分散在血管中。我们,因此,在本研究中研究了剪切流对循环CRC细胞的影响。CRC细胞系SW620分别经受12.5达因/cm2的剪切流1和2小时。所产生的升高的caspase-9和-3表明剪切流引发了SW620的凋亡。与较高水平的细胞周期蛋白D1相关的细胞增大与流式细胞术结果一致，表明细胞周期停滞在G1期。升高的荧光粉eNOSS1177增加了一氧化氮的产生，并导致活性氧介导的氧化应激。剪切流还通过增加E-cadherin和ZO-1同时减少Snail和Twist1来调节上皮-间质转化（EMT）。剪切的SW620的迁移和侵入也大大减少。进一步的研究表明，线粒体膜电位明显降低，而线粒体质量和ATP产生没有改变。除了12.5达因/cm2的剪切流量外，还比较了较低（6.25达因/cm2）和较高（25达因/cm2）剪切流量下的EMT表达式。结果表明，较低的剪切流量增加了间充质特征，较高的剪切流量增加了上皮特征。剪切流降低CRC在其转移扩散中的恶性,这开辟了通过应用机械剪切流装置来改善癌症治疗的新方法。
