Abstract
Effective chemotherapy drugs for cancer that would inhibit tumor growth and suppress metastasis are currently lacking. In this study, a series of arene ruthenium complexes, [(η6-arene)Ru(H2iip)Cl]Cl (arene = p-cymene, RAWQ03; CH3C6H5, RAWQ04; and C6H6, RAWQ11), were synthesized and their inhibitory activity against tumor cells were evaluated. The results showed that the complex RAWQ11 inhibited the growth of MDA-MB-231 breast cancer cells by inducing S-phase arrest, which is closely related to the inhibition of cell mitosis-mediated cell nucleus damage. Further studies showed that RAWQ11 can inhibit the invasion and metastasis of MDA-MB-231 cells. The morphology of MDA-MB-231 cells changed, the number of focal adhesions decreased, and the stress fibers de-polymerized upon dealing with the complex RAWQ11. The FITC-gelatin assay confirmed that the formation of invadopodia in MDA-MB-231 cells was significantly blocked by RAWQ11. Furthermore, RAWQ11 can block the AKT signal pathway by upregulating the PTEN expression through binding and downregulating miR-21. These results demonstrated that this type of arene ruthenium(ii) complex can block the invadopodia formation by regulating the PTEN/AKT signal pathway mediated by miR-21 to inhibit the invasion and metastasis of breast cancer cells. Therefore, this complex can be used as a potential dual functional agent to inhibit the growth and metastasis of tumor cells.