Wagenblast Jens, Hirth Daniel, Eckardt Anne, Leinung Martin, Diensthuber Marc, Stöver Timo, Hambek Markus
ENT Department, Medical School, Goethe University, D-60590 Frankfurt am Main, Germany.
Mol Clin Oncol. 2013 Mar;1(2):286-290. doi: 10.3892/mco.2012.45. Epub 2012 Nov 27.
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 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.
在多种血液学和实体瘤模型中，抑制polo样激酶1（PLK-1）已被证明是有效的。在这项系统性研究中，研究了PLK-1小分子抑制剂BI2536与顺铂和多西他赛联合使用时对9种鳞状细胞癌细胞系的抗肿瘤作用，其中大多数起源于头颈部（SCCHN）。使用BI2536、顺铂和多西他赛，以细胞系特异性浓度对9种SCCHN细胞系进行了剂量递增研究。使用细胞组织学和人凋亡阵列试剂盒定量测量生长抑制和促凋亡作用。与单独使用顺铂或多西他赛相比，BI2536与顺铂和多西他赛联合使用在研究的SCCHN细胞系中显示出明显更高的抗增殖和凋亡活性（P≤0.008）。本研究结果表明，与单独使用顺铂或多西他赛相比，在传统化疗药物中添加PLK-1抑制剂BI2536在SCCHN细胞系中导致了统计学上更高的抗增殖和凋亡作用。在临床环境中引入BI2536可能会增强传统药物的抗肿瘤活性，可能会降低癌症治疗的毒性副作用。
