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西妥昔单抗抑制顺铂诱导的食管鳞状细胞癌中表皮生长因子受体(EGFR)信号通路的激活。

Cetuximab inhibits cisplatin-induced activation of EGFR signaling in esophageal squamous cell carcinoma.

作者信息

Kwon Junhye, Yoon Hyeon-Joon, Kim Ji-Hee, Lee Tae Sup, Song In Ho, Lee Hae Won, Kang Moon Chul, Park Jong Ho

机构信息

Department of Translational Research, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.

Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.

出版信息

Oncol Rep. 2014 Sep;32(3):1188-92. doi: 10.3892/or.2014.3302. Epub 2014 Jul 3.

Abstract

A malignant esophageal cancer, squamous cell carcinoma is one of the most prevalent cancers. Despite the use of present surgical techniques combined with various treatment modalities, the overall 5-year survival rate remains at 15-34%. Epidermal growth factor receptor (EGFR) is the most well studied receptor in various cancers and EGFR overexpression is detected in 40% of esophageal squamous cell carcinomas (ESCCs) and ESCC cell lines. To examine the EGFR antibody combination effect, we used treatment with cisplatin and cetuximab in ESCC cell lines, TE-4 and TE-8. Combination of cetuximab and cisplatin resulted in a growth inhibition only in the EGFR overexpressed TE-8 cell line. Furthermore, we confirmed that cisplatin-induced EGFR activation was inhibited by cetuximab in TE-8 but not in TE-4 cells. Our data suggest that cetuximab combined with cisplatin exerts antitumorigenic effects in vitro and in vivo via suppression of EGF signaling, which can be applied toward targeted ESCC treatments.

摘要

恶性食管癌,鳞状细胞癌是最常见的癌症之一。尽管采用了目前的手术技术并结合各种治疗方式,但总体5年生存率仍维持在15% - 34%。表皮生长因子受体(EGFR)是各类癌症中研究最为深入的受体,在40%的食管鳞状细胞癌(ESCC)及ESCC细胞系中可检测到EGFR过表达。为研究EGFR抗体联合用药的效果,我们在ESCC细胞系TE - 4和TE - 8中使用顺铂和西妥昔单抗进行治疗。西妥昔单抗与顺铂联合使用仅在EGFR过表达的TE - 8细胞系中导致生长抑制。此外,我们证实西妥昔单抗在TE - 8细胞中可抑制顺铂诱导的EGFR激活,但在TE - 4细胞中则不然。我们的数据表明,西妥昔单抗联合顺铂通过抑制EGF信号在体外和体内发挥抗肿瘤作用,这可应用于靶向ESCC治疗。

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