Role of FOXO3A in trastuzumab combination chemotherapy in esophageal squamous cell carcinoma

Masashi Takahashi, Kazumasa Fukuda, Yoshiro Saikawa, Rieko Nakamura, Norihito Wada, Hirofumi Kawakubo, Hiroya Takeuchi, Yuko Kitagawa

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1921-1930
Number of pages10
JournalAnticancer research
Volume40
Issue number4
DOIs
Publication statusPublished - 2020 Apr

Keywords

  • Esophageal squamous cell carcinoma
  • FOXO3A
  • HER2
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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