Prewett M, Rockwell P, Rose C, Goldstein N
IMCLONE SYST INC,DEPT IMMUNOL,NEW YORK,NY 10014.
Int J Oncol. 1996 Aug;9(2):217-24. doi: 10.3892/ijo.9.2.217.
Overexpression of the epidermal growth factor receptor (EGFR) has been found to correlate with a poor prognosis for many cancers. The EGFR appears to play an important role in regulating cell growth during tumorigenesis and blockade of the EGFR/ligand interaction may be a means of inducing cell cytotoxicity, terminal differentiation, or apoptosis. In this report, we show that the growth of well-established xenografts of the human epidermoid carcinoma cell line KB could be significantly inhibited by the combination of cisplatin plus C225, a chimeric anti-EGFR monoclonal antibody, whereas the individual treatments had no effect on tumor growth. Substantive changes in the protein expression levels of the EGFR as well as several important cell cycle regulatory proteins were found in cells treated with the combination. In addition, cisplatin plus C225 inhibited the overall phosphorylation patterns including EGFR activation. These in vitro data suggest a mechanism of action for the in vivo therapeutic effects of C225 plus cisplatin.
表皮生长因子受体（EGFR）的过表达已被发现与许多癌症的不良预后相关。EGFR似乎在肿瘤发生过程中调节细胞生长方面发挥重要作用，阻断EGFR/配体相互作用可能是诱导细胞毒性、终末分化或凋亡的一种手段。在本报告中，我们表明，顺铂加C225（一种嵌合抗EGFR单克隆抗体）的联合使用可显著抑制人表皮样癌细胞系KB成熟异种移植物的生长，而单独治疗对肿瘤生长没有影响。在用联合药物处理的细胞中，发现EGFR以及几种重要的细胞周期调节蛋白的蛋白质表达水平发生了实质性变化。此外，顺铂加C225抑制了包括EGFR激活在内的整体磷酸化模式。这些体外数据提示了C225加顺铂体内治疗效果的作用机制。
