BI6727, A Polo-like Kinase1Inhibitor, Enhances Taxol Chemosensitivity In Human Ovarian Cancer Cells

Objective：Polo-like kinase1(Plk1) plays an important role in different stages of mitosis. Manyinvestigations have established that Plk1is a prime target candidate for drug developmentin cancer.Taxol is one of the most commonly used chemotherapy drugs in treatment ofovarian cancer.However, the taxol resistance has been a fundamental problem in cancermanagement and is the primary reason for treatment failure.Thus, we tested the effect ofPlk1inhibitorBI6727alone and in combination with taxol on the growth of ovarian cancer cells to searchfor effective and safe anticancer regimens.Methods：(1) Immunohistochemical method was used to detect PLK1expression in normal ovarianand ovarian cancer tissue;(2) CCK-8assay was used to explore concentration regularity of BI6727single-agenttreatment on ovarian cancer cells;(3) CCK-8assay, plate clone formation assay and flow cytometry were adopted tomeasure BI6727and Taxol combination effect on ovarian cancer cells;(4) Mechanism of BI6727and Taxol combination effect was detected by Westernblotting.Results：(1) PLK1expression in ovarian cancer tissue is higher than in normal ovarian tissue. WithDAB staining scoring standard, mean score in ovarian cancer and normal ovariantissue respectively is199±44,133+22（P <0.05). (2) With the elevated concentration of BI6727on SKOV3、 OV2008and A2780, theinhibition effect of cell proliferation increased. When BI6727is1nM and10nM, theinhibition effect is not obvious; But50nM, the inhibition effect enhanced obviously;≥500nM, the inhibition effect of trend is no longer obvious.(3) BI6727and Taxol have a synergy cytotoxic effect. Combining with10nM Taxol,cytotoxicity increases obviously. When Taxol is100nM, the cytotoxic effect of Taxolalone or combination with BI6727has no obvious difference.Comparing withBI6727alone and Taxol alone, the percentage of apoptosis cell of combined applicationhas statistical significance.(4) Western blotting showed that cleaved PARP、Bax、Cyclin B1and H3P expressionincreased, and bcl-xl expression obviously decreased.Conclusion:PLK1might be an effective target of taxol sensitivity. For a synergistic promotion ofthe anticancer effect of taxol, low doses of BI6727is sufficient. Thus, taxol combined withlow doses of BI6727improves the toxicity profile risk associated with a potent antitumoractivity and improves clinical concepts for the treatment of ovarian cancer.