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表皮生长因子受体表达对头颈癌细胞西妥昔单抗和帕尼单抗反应率的影响。

Influence of epidermal growth factor receptor expression on the cetuximab and panitumumab response rates of head and neck carcinoma cells.

作者信息

Hartmann Stefan, Seher Axel, Brands Roman C, Linz Christian, Lessner Grit, Böhm Hartmut, Kübler Alexander C, Müller-Richter Urs D A

机构信息

Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.

Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.

出版信息

J Craniomaxillofac Surg. 2014 Oct;42(7):1322-8. doi: 10.1016/j.jcms.2014.03.018. Epub 2014 Apr 2.

Abstract

OBJECTIVES

To examine the impact of epidermal growth factor receptor (EGFR) expression level on the efficacy of monoclonal antibodies against the EGFR.

METHODS

In four human head and neck carcinoma cell lines, epidermal growth factor expression was knocked down by lentiviral RNA interference. Next, the efficacies of cetuximab and panitumumab at concentrations of 4, 40, and 400 μg/ml were measured by real time cell analysis for a 48-h duration. Finally, the different response rates to the drugs were statistically analyzed.

RESULTS

The lentiviral EGFR knockdown efficiency ranged from 18 to 54 % across all of the cell lines. All original cell lines exhibited rather poor or inverse responses with regard to EGFR-AB treatment. In contrast, inhibiting EGFR expression in the same cell lines yielded statistically significant better responses to cetuximab or panitumumab treatment.

CONCLUSIONS

The cell lines used in this study responded poorly to cetuximab and panitumumab. Better anti-EGFR treatment efficacy was related to lower EGFR expression in head and neck cancer cell lines. These findings might influence the selection of patients to receive cetuximab and panitumumab treatment for head and neck cancer.

摘要

目的

研究表皮生长因子受体(EGFR)表达水平对表皮生长因子受体单克隆抗体疗效的影响。

方法

在四种人源头颈癌细胞系中,通过慢病毒RNA干扰敲低表皮生长因子的表达。接下来,采用实时细胞分析技术,测定西妥昔单抗和帕尼单抗在4、40和400μg/ml浓度下作用48小时的疗效。最后,对药物的不同反应率进行统计学分析。

结果

在所有细胞系中,慢病毒介导的EGFR敲低效率在18%至54%之间。所有原始细胞系对EGFR抗体治疗均表现出较差或相反的反应。相比之下,在相同细胞系中抑制EGFR表达,对西妥昔单抗或帕尼单抗治疗产生了具有统计学意义的更好反应。

结论

本研究中使用的细胞系对西妥昔单抗和帕尼单抗反应较差。更好的抗EGFR治疗疗效与头颈癌细胞系中较低的EGFR表达有关。这些发现可能会影响头颈癌患者接受西妥昔单抗和帕尼单抗治疗的选择。

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