Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany.
Oncol Rep. 2011 Apr;25(4):1145-51. doi: 10.3892/or.2011.1153. Epub 2011 Jan 18.
Squamous cell carcinoma of the head and neck (HNSCC) is the most common neoplasm arising in the upper aerodigestive tract. Unfortunately, the survival for this type of cancer has not improved significantly in the past 25 years. To enhance the survival rate multimodal therapy regimens have been set up. In these regimens chemotherapy plays a pivotal role in the majority of advanced cases. Transmembrane protein- tyrosine kinases (PTK) are fundamental elements of the signal transduction. In consequence, they might be promising targets for cancer therapy. Imatinib (STI 571) was originally designed to inhibit the BCR-ABL tyrosine kinase in chronic myeloid leukemia. But imatinib also has an inhibitory impact on the PTK receptor c-kit and on its PTK activity. Furthermore, growth and invasion of HNSCC are strongly influenced by the extracellular matrix (ECM). The ECM is altered by matrix metalloproteinases (MMP). In this study, we incubated different HNSCC cell lines with rising concentrations of imatinib and/or carboplatin. After an incubation time of up to 10 days, we evaluated c-kit, MMP-2 and MMP-14 by ELISA techniques and immunohistochemical methods. Especially the combination of 7.5 μmol carboplatin with 30 μmol imatinib resulted in a significant decrease in MMP-2 expression in all observed cell lines (p<0.05). We did not demonstrate a significant alteration in c-kit expression by imatinib and carboplatin. We observed an increase in apoptosis in HNSCC cells by the combination of the two observed chemotherapeutic drugs. In all cell lines tested, expression of c-kit and MMP could be demonstrated. Our results indicate that MMP-2 expression was suppressed in the presence of imatinib. Thus, imatinib may exert in part its inhibitory effect on malignant cell growth via the blockage of the signal transduction of PTK receptors. Further studies are warranted, especially one keeping in mind the moderate toxicity of imatinib.
头颈部鳞状细胞癌（HNSCC）是上呼吸道最常见的肿瘤。不幸的是，在过去的 25 年中，这种癌症的生存率并没有显著提高。为了提高生存率，已经制定了多模式治疗方案。在这些方案中，化疗在大多数晚期病例中起着关键作用。跨膜蛋白酪氨酸激酶（PTK）是信号转导的基本要素。因此，它们可能是癌症治疗的有前途的靶点。伊马替尼（STI571）最初是为了抑制慢性髓性白血病中的 BCR-ABL 酪氨酸激酶而设计的。但伊马替尼也对 PTK 受体 c-kit 及其 PTK 活性有抑制作用。此外，HNSCC 的生长和侵袭受到细胞外基质（ECM）的强烈影响。细胞外基质由基质金属蛋白酶（MMP）改变。在这项研究中，我们用不同浓度的伊马替尼和/或卡铂孵育不同的 HNSCC 细胞系。孵育时间长达 10 天后，我们通过 ELISA 技术和免疫组织化学方法评估 c-kit、MMP-2 和 MMP-14。特别是 7.5μmol 卡铂与 30μmol 伊马替尼联合使用，导致所有观察到的细胞系中 MMP-2 表达显著下降（p<0.05）。我们没有证明伊马替尼和卡铂对 c-kit 表达有显著改变。我们观察到两种观察到的化疗药物联合使用可增加 HNSCC 细胞的凋亡。在所有测试的细胞系中，都可以证明 c-kit 和 MMP 的表达。我们的结果表明，在伊马替尼存在的情况下，MMP-2 的表达受到抑制。因此，伊马替尼可能通过阻断 PTK 受体的信号转导，部分发挥其对恶性细胞生长的抑制作用。需要进一步的研究，特别是考虑到伊马替尼的中度毒性。
