Osteosarcoma is the most common type of primary
bone cancer in children and adolescents. Treatment options for
osteosarcoma may include surgery,
chemotherapy, and
radiotherapy. Unfortunately, many patients eventually relapse, resulting in an unsatisfactory outcome. The
serine/
threonine-specific
polo-like kinase 1 (PLK1) is a
kinase that plays an important role in mitosis and the maintenance of
genomic stability. PLK1 has been found to be highly expressed in the malignant cells of
osteosarcoma. Here, we describe the in-vitro and in-vivo effects of
BI 2536, a small-molecule inhibitor of PLK1, which through inhibiting PLK1 enzymatic activity, causes mitotic arrest and eventually induces
cancer cell apoptosis. In this study, we show that the PLK1 inhibitor,
BI 2536, inhibits proliferation and induces apoptosis in two-dimensional and three-dimensional cultures of
osteosarcoma cell lines, KHOS and U-2OS. A proliferation assay performed both in two-dimensional and three-dimensional culture showed that the growth of both cell lines was inhibited by
BI 2536. Cell cycle analysis showed that the cells treated with
BI 2536 were mainly arrested in the G2/M phase. Immunofluorescence and western blotting analysis confirmed that the administration of
BI 2536 led to significant decrease of PLK1 and Mcl-1
protein expression levels in dose-dependent and time-dependent manners. Furthermore, BI 2536-induced apoptosis in the
osteosarcoma cell lines was shown by
poly (ADP-ribose) polymerase cleavage and
caspase assay. Finally, in mouse
osteosarcoma xenografts, BI 2536-treated mice had significantly smaller
tumors compared with the control mice. These findings offer evidence of the potential role for targeting PLK1 in
osteosarcoma therapy.