Vindin Howard, Bischof Leanne, Gunning Peter, Stehn Justine
1Oncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
J Biomol Screen. 2014 Mar;19(3):354-68. doi: 10.1177/1087057113503494. Epub 2013 Sep 9.
The actin cytoskeleton plays an important role in most, if not all, processes necessary for cell survival. Given the fundamental role that the actin cytoskeleton plays in the progression of cancer, it is an ideal target for chemotherapy. Although it is possible to image the actin cytoskeleton in a high-throughput manner, there is currently no validated method to quantify changes in the cytoskeleton in the same capacity, which makes research into its organization and the development of anticytoskeletal drugs difficult. We have validated the use of a linear feature detection algorithm, allowing us to measure changes in actin filament organization. Its ability to quantify changes associated with cytoskeletal disruption will make it a valuable tool in the development of compounds that target the cytoskeleton in cancer. Our results show that this algorithm can quantify cytoskeletal changes in a cell-based system after addition of both well-established and novel anticytoskeletal agents using either fluorescence microscopy or a high-content imaging approach. This novel method gives us the potential to screen compounds in a high-throughput manner for cancer and other diseases in which the cytoskeleton plays a key role.
肌动蛋白细胞骨架在细胞存活所需的大多数（即便不是全部）过程中发挥着重要作用。鉴于肌动蛋白细胞骨架在癌症进展中所起的基础性作用，它是化疗的理想靶点。尽管可以以高通量方式对肌动蛋白细胞骨架进行成像，但目前尚无经过验证的方法能够以同样的能力量化细胞骨架的变化，这使得对其组织结构的研究以及抗细胞骨架药物的开发变得困难。我们已经验证了一种线性特征检测算法的用途，它使我们能够测量肌动蛋白丝组织的变化。其量化与细胞骨架破坏相关变化的能力，将使其成为开发针对癌症中细胞骨架的化合物的有价值工具。我们的结果表明，该算法能够在添加成熟的和新型抗细胞骨架药物后，使用荧光显微镜或高内涵成像方法，在基于细胞的系统中量化细胞骨架的变化。这种新方法使我们有可能以高通量方式筛选针对癌症和其他细胞骨架起关键作用的疾病的化合物。
