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Evaluation of Polo‐like kinase 1 as a potential therapeutic target in Merkel cell carcinoma
Author(s) -
Kadletz Lorenz,
Bigenzahn Johannes,
Thurnher Dietmar,
Stanisz Isabella,
Erovic Boban M.,
Schneider Sven,
Schmid Rainer,
Seemann Rudolf,
Birner Peter,
Heiduschka Gregor
Publication year - 2016
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.24349
Subject(s) - merkel cell carcinoma , plk1 , cancer research , merkel cell , cisplatin , flow cytometry , cell growth , apoptosis , cell culture , medicine , viability assay , biology , pathology , cell cycle , carcinoma , chemotherapy , immunology , biochemistry , genetics
Background Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin. Treatment options for MCC include surgery, radiotherapy, and chemotherapy. The purpose of this study was to assess the expression of Polo‐like kinase 1 (PLK1) in MCC and the role of the inhibitor, BI2536, as a potential therapeutic option in MCC. Methods PLK1 expression was assessed in tissue samples from 28 patients with MCC and 5 healthy skin samples via immunohistochemistry and furthermore in the 2 MCC cell lines, MCC13 and MCC26, via immunoblotting. The impact of increasing doses of BI2536 alone and in combination with cisplatin or irradiation on cell viability was measured using the CCK‐8 assay. Colony forming assays were performed to evaluate long‐term effects of combination treatments. Additionally, the induction of apoptotic cell death was measured via flow cytometry. Results PLK1 is moderately to strongly expressed in 75% of the patients with MCC. The PLK1 inhibitor, BI2536, demonstrated marked inhibition of cell proliferation with IC 50 in the low nM range (from 10.07–12.39 nM). Furthermore, BI2536 induces apoptosis in MCC cell lines and acts synergistically in combination with irradiation and cisplatin. Conclusion Because of the marked upregulation of PLK1 in MCC tumor samples and potent inhibition of cell proliferation using a specific clinically available inhibitor, targeting of PLK1 qualifies as a potential novel therapeutic strategy in MCC. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E1918–E1925, 2016