Cell motility has been implicated in the spreading and metastasis of cancer cells. Actin cytoskeleton plays a major role in regulation of the cell migration and adhesion. Thus, the discovery of drug candidates acting on new targets which regulate actin cytoskeleton, shall be able to address the problem of cancer metastasis by modifying cancer cell migration ability of. In this study,1,3-benzodioxol-5-yl[1-(5- isoquinolinylmethyl)-3-piperidinyl]methanone(R3)was identified as a novel potent ROCK2 inhibitor. Effects of R3on cell morphology, adhesion, cell migration and actin filaments in human neuroblastoma SH-SY5Y cells and PC12 cells were studied. Exposure of SH-SY5Y cells to R3 led to significant changes in cell shape and a decrease in actin stress fibers, adhesions and migration. Further experiments demonstrated that R3 was able to significantly inhibit phosphorylation of cofilin, a regulator protein for actin stress fibers. Taken together, these results suggest thatR3 inhibits migration of human neuroblastomaSH-SY5Y cells through regulation of stress fibersand ROCK/cofilin pathway.

細胞的移動能力與腫瘤的擴散和轉移的過程有所關連，在細胞遷移和粘附的過 程中，肌動蛋白細胞骨架起著關鍵性的作用。因此，開發針對能調節細胞骨架 的新藥物靶點的抑制劑，藉由調節癌細胞的移動能力進一步抑制癌細胞的轉移。 在這項研究中，1,3-苯並二氧雜環戊烯-5-基[1-（5- isoquinolinylmethyl）-3-呱啶 基]甲酮 (R3)被確定為一個新的有效的 ROCK2 抑製劑的藥物。在人神經母細胞 瘤 SH-SY5Y 細胞暴露於 R3 後，研究其細胞形態，粘附，細胞遷移和肌動蛋白 絲的變化。結果顯示 SH-SY5Y 細胞暴露於 R3 後，導致了細胞形狀和肌動蛋白 應力纖維的顯著變化，並降低了粘連和遷移的能力。進一步的實驗表明，R3 能 夠顯著抑制磷酸化絲切蛋白，調節蛋白的肌動蛋白應力纖維，這些結果表明， 抑制 ROCK 途徑在抗遷移作用的調控中起了重要的角色。