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Antitumoral effect of PLK-1-inhibitor BI2536 in combination with cisplatin and docetaxel in squamous cell carcinoma cell lines of the head and neck
Author(s) -
Jens Wagenblast,
D Hirth,
Änne Eckardt,
Martin Leinung,
Marc Diensthuber,
Timo Stöver,
Markus Hambek
Publication year - 2012
Publication title -
molecular and clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.442
H-Index - 7
eISSN - 2049-9469
pISSN - 2049-9450
DOI - 10.3892/mco.2012.45
Subject(s) - docetaxel , cisplatin , cancer research , head and neck squamous cell carcinoma , cancer , apoptosis , oncogene , cell culture , molecular medicine , hematology , medicine , cell cycle , oncology , head and neck cancer , pathology , biology , chemotherapy , genetics , biochemistry
Inhibition of the polo-like-kinase-1 (PLK-1) has been shown to be effective in several haematological and solid tumor models. In this systemic in vitro study, the antitumor effect of BI2536, a small molecule inhibitor of PLK-1, in combination with cisplatin and docetaxel was examined in nine squamous cell carcinoma cell lines, most of which had a head and neck origin (SCCHN). Dose escalation studies were conducted with nine SCCHN cell lines using BI2536, cisplatin and docetaxel in cell line-specific concentrations. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and a Human Apoptose Array kit. BI2536 in combination with cisplatin and docetaxel showed a markedly higher antiproliferative and apoptotic activity in the SCCHN cell lines investigated (P≤0.008), compared with single agent cisplatin or docetaxel alone. The findings of this study showed that the addition of PLK-1-inhibitor BI2536 to conventional chemotherapeutic drugs led to a statistically higher antiproliferative and apoptotic effect in SCCHN cell lines compared with cisplatin or docetaxel alone. Inaugurating BI2536 in the clinical setting might enhance the antitumoral activity of conventional drugs, possibly leading to less toxic side effects of cancer therapy.

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