Role of FOXO3A in Trastuzumab Combination Chemotherapy in Esophageal Squamous Cell Carcinoma

被引：2
作者：
Takahashi, Masashi [1 ]
Fukuda, Kazumasa [1 ]
Saikawa, Yoshiro [1 ]
Nakamura, Rieko [1 ]
Wada, Norihito [1 ]
Kawakubo, Hirofumi [1 ]
Takeuchi, Hiroya [2 ]
Kitagawa, Yuko [1 ]
机构：
[1] Keio Univ, Sch Med, Dept Surg, Tokyo, Japan
[2] Hamamatsu Univ Sch Med, Dept Surg, Hamamatsu, Shizuoka, Japan
来源：
ANTICANCER RESEARCH | 2020年 / 40卷 / 04期
关键词：
FOXO3A; HER2; trastuzumab; esophageal squamous cell carcinoma; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; MOLECULAR SUBTYPES; RAS MUTATIONS; OPEN-LABEL; TRIAL; EFFICACY; PLUS; KRAS;
D O I：
10.21873/anticanres.14147
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background/Aim: Targeting of the human epidermal growth factor receptor 2 (HER2) is suggested to be beneficial for esophageal squamous cell carcinoma (ESCC) patients with HER2 amplification. In this study, we evaluated the effects of combination chemotherapy with HER2-targeted drug trastuzumab in ESCC cells and examined the underlying mechanism contributing to these effects. Materials and Methods: HER2 expression was verified, and the efficacy of chemotherapy with and without trastuzumab was investigated in vitro and in vivo. Results: The combination of trastuzumab and a combined-modality therapy stimulated the PI3K/Akt pathway in ESCC cells overexpressing HER2. Trastuzumab treatment resulted in the intranuclear accumulation of FOXO3A in ESCC xenografts overexpressing HER2. The combination of trastuzumab and a combined-modality therapy enhanced antitumor effects in HER2-overexpressing ESCC xenografts. Conclusion: FOXO3A plays an important role in mediating the effects of trastuzumab, and combination chemotherapy may be a promising treatment for patients with HER2-overexpressing ESCC.
引用
收藏
页码：1921 / 1930
页数：10
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