Erjala Kaisa, Raitanen Misa, Kulmala Jarmo, Grénman Reidar
Department of Otorhinolaryngology, Head and Neck Surgery, Turku University Central Hospital, 20520 Turku, Finland.
J Cancer Res Clin Oncol. 2007 Mar;133(3):169-76. doi: 10.1007/s00432-006-0154-0. Epub 2006 Oct 5.
Squamous cell carcinoma of the head and neck (HNSCC) remains a clinical challenge because of the high rate of locoregional disease recurrence. Standard treatment includes surgery, radiation, chemoradiation or a combination of these approaches. New therapies are needed to achieve improved survival, quality of life and organ function in these patients. A novel molecular targeted therapy incorporated into our current treatment strategies may have a significant role in the treatment of HNSCC. The aim of this study was to evaluate the sensitivity of HNSCC cell lines to vinorelbine combined with gefitinib in vitro.
Six recently established cell lines were used: UT-SCC-9, -11, -19A, -29 and -34 (laryngeal SCC) and UT-SCC-33 (oral cavity SCC). Chemosensitivity was tested using the 96-well plate clonogenic assay. The vinorelbine concentrations used varied between 0.4 and 1.0 nM and the gefitinib concentrations varied between 0.05 and 1.6 muM. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the two drugs to the survival fraction (SF) of gefitinib alone.
In the current study the combination of vinorelbine and gefitinib had a clear supra-additive or additive cytotoxic effect on the HNSCC cell lines.
This finding is encouraging as a proof of the possible benefit of combing an EGFR targeting compound with a cell cycle specific drug and warrants further studies of available combinations in vitro.
头颈部鳞状细胞癌（HNSCC）由于局部区域疾病复发率高，仍然是一项临床挑战。标准治疗包括手术、放疗、放化疗或这些方法的联合应用。需要新的疗法来提高这些患者的生存率、生活质量和器官功能。将一种新型分子靶向疗法纳入我们当前的治疗策略可能在HNSCC的治疗中发挥重要作用。本研究的目的是在体外评估HNSCC细胞系对长春瑞滨联合吉非替尼的敏感性。
使用六种最近建立的细胞系：UT-SCC-9、-11、-19A、-29和-34（喉鳞状细胞癌）以及UT-SCC-33（口腔鳞状细胞癌）。使用96孔板克隆形成试验测试化学敏感性。所用长春瑞滨的浓度在0.4至1.0 nM之间变化，吉非替尼的浓度在0.05至1.6 μM之间变化。生存数据拟合到线性二次模型，并通过数值积分获得曲线下面积（AUC）值。通过比较两种药物的AUC比值与单独使用吉非替尼的生存分数（SF）来确定相互作用类型。
在本研究中，长春瑞滨和吉非替尼的联合对HNSCC细胞系具有明显的超相加或相加细胞毒性作用。
这一发现令人鼓舞，证明了将一种表皮生长因子受体（EGFR）靶向化合物与一种细胞周期特异性药物联合使用可能具有益处，并值得进一步在体外研究可用的联合方案。
