Accurate cell division relies on the behavior of well-balanced protein kinases including Polo-like kinases and Aurora kinases. Polo-like kinase 1 (PLK1) has essential roles in cell division. As an early trigger for G₂/M transition, PLK1 can phosphorylate and activate CDC25, the phosphatase, which can dephosphorylate and activate Cyclin B1-CDK1 complex and drive the mitotic progression. Aurora kinase A and B (AURKA and AURKB) are the main family members of Aurora kinases, which have functions in mitotic regulation. As these kinases are up-regulated in several human cancers, small molecular inhibitors which can specifically target the kinases are invented for anti-cancer therapies in clinical application. Since PLK1 and Aurora kinases have both unique and overlapped functions during the c...[ Read more ]

Accurate cell division relies on the behavior of well-balanced protein kinases including Polo-like kinases and Aurora kinases. Polo-like kinase 1 (PLK1) has essential roles in cell division. As an early trigger for G₂/M transition, PLK1 can phosphorylate and activate CDC25, the phosphatase, which can dephosphorylate and activate Cyclin B1-CDK1 complex and drive the mitotic progression. Aurora kinase A and B (AURKA and AURKB) are the main family members of Aurora kinases, which have functions in mitotic regulation. As these kinases are up-regulated in several human cancers, small molecular inhibitors which can specifically target the kinases are invented for anti-cancer therapies in clinical application. Since PLK1 and Aurora kinases have both unique and overlapped functions during the cell cycle, whether the co-inhibition of the kinases enhances mitotic catastrophe remains to be determined. In HeLa cells, we found that PLK1 inhibitor (BI-2536) induced different effects when combined together with AURKA or AURKB inhibitors (VX-689 and Barasertib respectively), either by causing mitotic arrest or promoting mitotic slippage. These synergistic effects can also be found in nasopharyngeal carcinoma cell lines, which is a highly invasive cancer in southern part of China and correlated with poor prognosis. More importantly, these cancer cells react more sensitively to co-inhibition of the kinases when comparing with normal nasopharyngeal epithelial cells. These observations may be implemented in cancer therapy in the near future, by using low dosages of combined drugs to specifically kill or arrest cancer cells without harming normal cells.