Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Institute Of Microbiology, Chinese Academy of Sciences, Beijing, China.
Phytother Res. 2019 Mar;33(3):618-630. doi: 10.1002/ptr.6250. Epub 2018 Dec 12.
Changes in cellular biomechanical properties affect cell migration and invasion. The natural compound Cucurbitacin B (CuB) has potent anticancer activity; however, the mechanism underlying its inhibitory effect on breast cancer metastasis needs further study. Here, we showed that low-dose CuB inhibited adhesion and altered the viscoelasticity of breast cancer cells, thereby, reducing cell deformability. In vitro and in vivo experiments proved that CuB effectively inhibited the migration and invasion of breast cancer cells. Further studies have found that CuB downregulated the expression of F-actin/vimentin/FAK/vinculin in breast cancer cells, altering the distribution and reorganization of cytoskeletal proteins in the cells. CuB inhibited signaling by the Rho family GTPases RAC1/CDC42/RhoA downstream of integrin. These findings indicate that CuB has been proven to mediate the reorganization and distribution of cytoskeletal proteins of breast cancer cells through RAC1/CDC42/RhoA signaling, which improves the mechanical properties of cell adhesion and deformation and consequently inhibits cell migration and invasion.
细胞生物力学特性的改变会影响细胞的迁移和侵袭。天然化合物葫芦素 B（CuB）具有很强的抗癌活性；然而，其抑制乳腺癌转移的机制仍需要进一步研究。在这里，我们表明低剂量的 CuB 抑制了乳腺癌细胞的黏附，并改变了其粘弹性，从而降低了细胞的变形性。体内外实验证明，CuB 能有效抑制乳腺癌细胞的迁移和侵袭。进一步的研究发现，CuB 下调了乳腺癌细胞中 F-肌动蛋白/波形蛋白/FAK/踝蛋白的表达，改变了细胞骨架蛋白在细胞中的分布和重排。CuB 抑制了整合素下游 Rho 家族 GTP 酶 Rac1/CDC42/RhoA 的信号转导。这些发现表明，CuB 通过 Rac1/CDC42/RhoA 信号转导，已被证明能介导乳腺癌细胞骨架蛋白的重排和分布，从而改善细胞黏附和变形的力学特性，进而抑制细胞迁移和侵袭。
