Sato Shinsuke, Kajiyama Yoshiaki, Sugano Masahiko, Iwanuma Yoshimi, Sonoue Hiroshi, Matsumoto Toshiharu, Sasai Keisuke, Tsurumaru Masahiko
Department of Gastrointestinal Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):203-11. doi: 10.1016/j.ijrobp.2004.05.017.
The role of HER-2/neu in the response of esophageal cancer to radiation is not well known. The purpose of this study was to evaluate the effect of an anti-HER-2/neu antibody trastuzumab on the proliferation, cell cycle distribution, and radiosensitivity of esophageal cancer cell lines.
Expression of HER-2/neu protein by four esophageal squamous cancer cell lines (KE4, TE8, TE9, and TE10) and an esophageal adenocarcinoma cell line (SKGT4) was assessed using immunohistochemical (IHC) analysis and flow cytometry. We also evaluated HER-2/neu oncogene expression by fluorescence in situ hybridization. As a control for HER-2/neu protein expression and gene amplification, breast cancer cell lines (MCF7, MDA MB175VII, and SKBR3) were also examined. The cytotoxity of trastuzumab (0.1-200 microg/mL) was estimated by the MTT assay, and the cell cycle distribution was determined by flow cytometry. The effect of 10 microg/mL trastuzumab combined with radiation was assessed by a clonogenic assay.
Flow cytometry and IHC revealed that two esophageal cancer cell lines (TE9 and SKGT4) showed HER-2/neu expression (IHC 1+ and mean fluorescence intensity of 11-20), while the other esophageal cancer cell lines were negative for HER-2/neu expression. Although trastuzumab alone had no effect on the esophageal cancer cell lines, the combination of 10 microg/mL trastuzumab with radiation showed a synergistic effect on the HER-2/neu expressing cell lines.
This study suggested that trastuzumab plus irradiation may be effective for the treatment of esophageal cancers, including adenocarcinoma and squamous cell cancer with HER-2/neu expression.
HER-2/neu在食管癌对放疗反应中的作用尚不清楚。本研究旨在评估抗HER-2/neu抗体曲妥珠单抗对食管癌细胞系增殖、细胞周期分布和放射敏感性的影响。
采用免疫组织化学（IHC）分析和流式细胞术评估四种食管鳞状癌细胞系（KE4、TE8、TE9和TE10）和一种食管腺癌细胞系（SKGT4）中HER-2/neu蛋白的表达。我们还通过荧光原位杂交评估HER-2/neu癌基因的表达。作为HER-2/neu蛋白表达和基因扩增的对照，还检测了乳腺癌细胞系（MCF7、MDA MB175VII和SKBR3）。通过MTT法评估曲妥珠单抗（0.1 - 200μg/mL）的细胞毒性，并通过流式细胞术确定细胞周期分布。通过克隆形成试验评估10μg/mL曲妥珠单抗联合放疗的效果。
流式细胞术和免疫组织化学显示，两种食管癌细胞系（TE9和SKGT4）显示HER-2/neu表达（免疫组织化学1+，平均荧光强度为11 - 20），而其他食管癌细胞系HER-2/neu表达为阴性。虽然单独使用曲妥珠单抗对食管癌细胞系没有影响，但10μg/mL曲妥珠单抗与放疗联合对HER-2/neu表达的细胞系显示出协同作用。
本研究表明，曲妥珠单抗联合放疗可能对治疗包括腺癌和具有HER-2/neu表达的鳞状细胞癌在内的食管癌有效。
