Kramer Benedikt, Kneissle Marcel, Birk Richard, Rotter Nicole, Aderhold Christoph
Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University Heidelberg, Manheim, Germany
Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University Heidelberg, Manheim, Germany.
Anticancer Res. 2018 May;38(5):2723-2731. doi: 10.21873/anticanres.12514.
BACKGROUND/AIM: Therapeutic options of locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) are limited. Src and cKIT are key protein regulators for local tumor progression. The aim of the study was to investigate the therapeutic potential of targeted therapies in human squamous cell carcinoma (HNSCC) in vitro. Therefore, the influence of the selective tyrosine kinase inhibitors niotinib, dasatinib, erlotinib, gefitinib and afatinib on Src and cKIT expression in Human papilloma virus (HPV)-positive and HPV-negative squamous cancer cells (SCC) was analyzed in vitro.
ELISA was performed to evaluate the expression of Src and cKIT under the influence of nilotinib, dasatinib, erlotinib, gefitinib and afatinib (10 μmol/l) in HPV-negative and HPV-positive SCC (24-96 h of incubation).
Gefitinib significantly increased cKIT expression in HPV-positive and HPV-negative cells whereas nilotinib and afatinib decreased cKIT expression in HPV-positive SCC. The influence of tyrosine kinase inhibitors in HPV-negative SCC was marginal. Surprisingly, Src expression was significantly increased by all tested tyrosine kinase inhibitors in HPV-positive SCC.
The results revealed beneficial and unexpected information concerning the interaction of selective tyrosine kinase inhibitors and the tumor biology of HNSCC.
背景/目的：局部晚期或转移性头颈部鳞状细胞癌（HNSCC）的治疗选择有限。Src和cKIT是局部肿瘤进展的关键蛋白调节因子。本研究的目的是在体外研究靶向治疗对人鳞状细胞癌（HNSCC）的治疗潜力。因此，在体外分析了选择性酪氨酸激酶抑制剂尼洛替尼、达沙替尼、厄洛替尼、吉非替尼和阿法替尼对人乳头瘤病毒（HPV）阳性和HPV阴性鳞状癌细胞（SCC）中Src和cKIT表达的影响。
采用酶联免疫吸附测定（ELISA）法评估尼洛替尼、达沙替尼、厄洛替尼、吉非替尼和阿法替尼（10μmol/l）作用下HPV阴性和HPV阳性SCC中Src和cKIT的表达（孵育24 - 96小时）。
吉非替尼显著增加HPV阳性和阴性细胞中的cKIT表达，而尼洛替尼和阿法替尼降低HPV阳性SCC中的cKIT表达。酪氨酸激酶抑制剂对HPV阴性SCC的影响很小。令人惊讶的是，所有测试的酪氨酸激酶抑制剂均显著增加HPV阳性SCC中的Src表达。
结果揭示了关于选择性酪氨酸激酶抑制剂与HNSCC肿瘤生物学相互作用的有益且意外的信息。
