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

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.