人乳头瘤病毒相关鳞状细胞癌中的酪氨酸激酶抑制揭示了cKIT和Src的有益表达。

Tyrosine Kinase Inhibition in HPV-related Squamous Cell Carcinoma Reveals Beneficial Expression of cKIT and Src.

作者信息

Kramer Benedikt, Kneissle Marcel, Birk Richard, Rotter Nicole, Aderhold Christoph

机构信息

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.

出版信息

Anticancer Res. 2018 May;38(5):2723-2731. doi: 10.21873/anticanres.12514.

DOI:10.21873/anticanres.12514

PMID:29715092

Abstract

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.

MATERIALS AND METHODS

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).

RESULTS

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.

CONCLUSION

The results revealed beneficial and unexpected information concerning the interaction of selective tyrosine kinase inhibitors and the tumor biology of HNSCC.

摘要

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。