ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells

被引:39
作者
Guerra, Fabiana Selos [1 ]
de Oliveira, Ramon Guerra [2 ]
Manssour Fraga, Carlos Alberto [2 ]
Mermelstein, Claudia dos Santos [3 ]
Fernandes, Patricia Dias [1 ]
机构
[1] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Farmacol Dor & Inflamacao, Rio De Janeiro, Brazil
[2] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Avaliacao & Sintese Subst Bioativas LASSBio, Rio De Janeiro, Brazil
[3] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Diferenciacao Muscular, Rio De Janeiro, Brazil
关键词
HEPATOCELLULAR-CARCINOMA; RHO; KINASES;
D O I
10.1038/s41598-017-14216-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 mu M, 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.
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页数:8
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