Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Rio de Janeiro, Brazil.
Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio®), Rio de Janeiro, Brazil.
Sci Rep. 2017 Oct 20;7(1):13723. doi: 10.1038/s41598-017-14216-z.
Tumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple-negative breast cancer (TNBC), is an aggressive type of breast cancer and associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell motility involving cytoskeleton regulation through stabilization of actin filaments and stress fiber formation. In this study we show that Fasudil, a ROCK inhibitor, inhibited the migration of MDA-MB 231 and A549 cells, without altering the viability of these cells at the concentration of 10 μM, modified tumor cell morphology, with disorganization of stress fibers and promotes activation of the canonical-Wnt/beta-catenin pathway. Therefore, Fasudil present a promising approach to the prevention of breast cancer metastasis through a different mechanism of action from the well-known one.
肿瘤侵袭性通常与转移有关。MDA-MB 231 是一种三阴性乳腺癌（TNBC），是一种侵袭性乳腺癌，与早期转移有关。Rho/ROCK 通路是细胞运动的关键调节剂，通过稳定肌动蛋白丝和形成应力纤维来调节细胞骨架。在这项研究中，我们表明，ROCK 抑制剂法舒地尔在 10 μM 的浓度下抑制 MDA-MB 231 和 A549 细胞的迁移，而不改变这些细胞的活力，改变肿瘤细胞形态，破坏应力纤维的组织并促进经典 Wnt/β-catenin 通路的激活。因此，法舒地尔通过与众所周知的机制不同的作用机制，为预防乳腺癌转移提供了一种很有前途的方法。
