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评估卡维林作为头颈部鳞状细胞癌(HNSCC)细胞系潜在化疗药物的作用。

Assessment of caroverine as a potential chemotherapeutical agent in HNSCC cell lines.

作者信息

Haymerle Georg, Thurnher Dietmar, Kadletz Lorenz, Stanisz Isabella, Brunner Markus, Kotowski Ulana, Enzenhofer Elisabeth, Heiduschka Gregor

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

出版信息

Eur Arch Otorhinolaryngol. 2015 Nov;272(11):3451-6. doi: 10.1007/s00405-014-3364-0. Epub 2014 Oct 29.

Abstract

Since the prognosis of head and neck squamous cell carcinoma (HNSCC) still remains poor, identifying novel chemotherapeutic agents is of outmost importance. The anticancer potential of quinoxalines has been described in various tumor entities. Caroverine, also a quinoxaline derivative, has been shown to suppress tumor promotion factors. The aim of this study was to evaluate the effect of caroverine on HNSCC cell lines. The HNSCC cell lines SCC9, SCC25, CAL27, and FaDu were incubated with caroverine alone or in combination with cisplatin, 5-fluorouracil (5-FU) or cetuximab. Cell viability was measured using the CCK-8 assay. The murine 3T3 fibroblast cell line was used to address tissue specificity. Apoptosis was visualized by immunohistochemistry. Caroverine showed a dose-dependent growth inhibition in all cell lines, IC50 values ranged from 75.69 to 179.80 µM. This effect was increased when caroverine was combined with cetuximab or 5-FU. Immunohistochemistry displayed more apoptosis after caroverine treatment compared to controls. Furthermore, caroverine alone had no growth inhibitory effect on 3T3 cells. For the first time, this study provides evidence that caroverine may serve as a supportive drug in the treatment of HNSCC patients.

摘要

由于头颈部鳞状细胞癌(HNSCC)的预后仍然很差,因此确定新型化疗药物至关重要。喹喔啉在各种肿瘤实体中的抗癌潜力已得到描述。卡维林也是一种喹喔啉衍生物,已被证明可抑制肿瘤促进因子。本研究的目的是评估卡维林对HNSCC细胞系的影响。将HNSCC细胞系SCC9、SCC25、CAL27和FaDu单独或与顺铂、5-氟尿嘧啶(5-FU)或西妥昔单抗联合用卡维林孵育。使用CCK-8测定法测量细胞活力。使用小鼠3T3成纤维细胞系来研究组织特异性。通过免疫组织化学观察细胞凋亡。卡维林在所有细胞系中均表现出剂量依赖性生长抑制,IC50值范围为75.69至179.80μM。当卡维林与西妥昔单抗或5-FU联合使用时,这种作用增强。与对照组相比,免疫组织化学显示卡维林处理后细胞凋亡更多。此外,卡维林单独对3T3细胞没有生长抑制作用。本研究首次提供证据表明,卡维林可能作为治疗HNSCC患者的辅助药物。

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