Department of Otorhinolaryngology, Tama-Hokubu Medical Center, Tokyo, Japan.
Int J Oncol. 2012 Jun;40(6):1805-12. doi: 10.3892/ijo.2012.1376. Epub 2012 Feb 16.
The epidermal growth factor receptor (EGFR) and related family member, HER-2, are often overexpressed simultaneously in patients with a variety of malignant tumors, and the combination may cooperatively promote cancer cell growth and survival. The purpose of this study was to examine antitumor effects of the combination treatment of cetuximab and trastuzumab on head and neck squamous cell carcinoma (HNSCC) using 16 HNSCC cell lines in terms of antiproliferative effect and antibody-dependent cell-mediated-cytotoxicity (ADCC). Previously we have reported the expression levels of EGFR mRNA on 16 HNSCC cell lines. All cell lines expressed mRNA for EGFR, HER-2 and HER-3; 12 cell lines expressed mRNA for HER-4; and 4 cell lines did not express mRNA for HER-4. In in vitro proliferation assay, the combination treatment of cetuximab and trastuzumab significantly lowered cell viability compared to either drug alone. The mRNA expression levels of EGFR and HER-2 were not correlated with the efficacy of the combination treatment of cetuximab and trastuzumab and the expression levels of HER-3 and HER-4 also showed no correlation with the efficacy of the combination treatment. We evaluated the gene status of HER-2 exons 23 and 24 in 16 HNSCC cell lines, but there was no mutation of HER-2 in any of the cell lines. Either drug showed ADCC in the 3 cell lines using peripheral blood mononuclear cells (PBMCs), however, a significant combination effect was not observed. Combined molecular targeted antibody drug therapy for EGFR and HER-2 may be useful in the treatment of HNSCC.
表皮生长因子受体 (EGFR) 和相关家族成员 HER-2 通常在多种恶性肿瘤患者中同时过表达，并且这种组合可能协同促进癌细胞的生长和存活。本研究的目的是使用 16 种头颈鳞状细胞癌 (HNSCC) 细胞系，从增殖抑制作用和抗体依赖细胞介导的细胞毒性 (ADCC) 两方面，研究西妥昔单抗和曲妥珠单抗联合治疗对头颈鳞状细胞癌的抗肿瘤作用。此前，我们已经报道了 16 种 HNSCC 细胞系中 EGFR mRNA 的表达水平。所有细胞系均表达 EGFR、HER-2 和 HER-3 的 mRNA；12 种细胞系表达 HER-4 的 mRNA；4 种细胞系不表达 HER-4 的 mRNA。在体外增殖试验中，与单独使用任何一种药物相比，西妥昔单抗和曲妥珠单抗联合治疗显著降低了细胞活力。EGFR 和 HER-2 的 mRNA 表达水平与西妥昔单抗和曲妥珠单抗联合治疗的疗效无关，HER-3 和 HER-4 的表达水平也与联合治疗的疗效无关。我们评估了 16 种 HNSCC 细胞系中 HER-2 外显子 23 和 24 的基因状态，但在任何细胞系中均未发现 HER-2 突变。两种药物在 3 种使用外周血单核细胞 (PBMC) 的细胞系中均显示出 ADCC，但未观察到显著的联合效应。针对 EGFR 和 HER-2 的联合分子靶向抗体药物治疗可能对 HNSCC 的治疗有用。
