PLk1 Inhibitor Volasertib Potently Synergizes With Cisplatin In Hepatocellular Carcinoma

Background: Hepatocellular carcinoma(HCC) is the sixth most frequent malignant tumor, and the third leading cause of cancer-related mortality in the world. The patients are usually diagnosed when tumor is in an advanced stage, and the poor 5-year survival. Thus, treatment of HCC remains an urgent health concern.Objective: To investigate the anti-tumor effect of volasertib alone or in combination with cisplatin on human hepatocellular carcinoma.Methods: The cytotoxic effect of drugs was measured by MTT assay. Durg-drug interactions were analyzed by the coefficient of drug interaction. Cell cycle and apoptosis were detected by flow cytometry. Morphologic changes were observed by fluorescence microscope. Protein expression was detected by western blotting. Model of subcutaneous xenograft in nude mice were used to study the antitumor effect in vivo.Results: Volasertib inhibited HCC cell lines growth in a dose- and time-dependent manner. Moreover, volasertib treatment induced cell cycle arrest at G2/M, spindle abnormalities and resulted in apoptosis. Combining volasertib with cisplatin resulted in synergistic antiproliferative effects on HCC cell lines.Conclusions: Our data demonstrate that inhibition of PLK1 by volasertib induced growth inhibition, cell cycle arrest and apoptosis in human HCC cell lines. Additionally, volasertib enhanced the anti-proliferative activity of cisplatin Thus, inhibiting PLK1 appears to be a potential treatment strategy in HCC.