Evaluation of Polo-like kinase 1 as a potential therapeutic target in Merkel cell carcinoma
Autor: | Lorenz Kadletz, Sven Schneider, Dietmar Thurnher, Rudolf Seemann, Gregor Heiduschka, Peter Birner, Isabella Stanisz, Johannes W. Bigenzahn, Rainer Schmid, Boban M. Erovic |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Cisplatin Pathology medicine.medical_specialty medicine.diagnostic_test Cell growth business.industry Merkel cell carcinoma food and beverages Cancer medicine.disease Flow cytometry 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Otorhinolaryngology Cell culture Apoptosis 030220 oncology & carcinogenesis medicine Cancer research Viability assay business medicine.drug |
Zdroj: | Head & Neck. 38:E1918-E1925 |
ISSN: | 1043-3074 |
DOI: | 10.1002/hed.24349 |
Popis: | 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 IC50 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, 2015 |
Databáze: | OpenAIRE |
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