Arsenic Trioxide Suppressed Migration and Angiogenesis by Targeting FOXO3a in Gastric Cancer Cells

International Journal of Molecular Sciences

Luo Gu¹  Lin Zhang¹  Lei Liu¹  Shining Zhan²  Yongping Wu²  Lili Chen²  Yueyuan Wang³  Jun Du³  Yujie Zhang³ 

[1] Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, China;Department of Pathology, Xuzhou Medical University, Xuzhou 221004, China;Department of Physiology, Nanjing Medical University, Nanjing211166, China;

关键词: As₂O₃;    FOXO3a;    gastric cancer;    migration;    angiogenesis;   

DOI  :  10.3390/ijms19123739

来源: DOAJ

【 摘 要 】

Arsenic trioxide (As₂O₃), a traditional remedy in Chinese medicine, has been used in acute promyelocytic leukemia (APL) research and clinical treatment. Previous studies have shown that As₂O₃ exerts its potent antitumor effects in solid tumors by regulating cell proliferation and survival. The aim of this study was to investigate whether As₂O₃ inhibited gastric cancer cell migration and angiogenesis by regulating FOXO3a expression. We found that As₂O₃ reduced gastric cancer cell viability in a dose-dependent manner and also inhibited cell migration and angiogenesis in vitro. Western blotting and immunofluorescence showed that As₂O₃ downregulated the levels of p-AKT, upregulated FOXO3a expression in the nucleus, and attenuated downstream Vascular endothelial growth factor (VEGF) and Matrix metallopeptidase 9 (MMP9) expression. Moreover, we demonstrated that knockdown of FOXO3a significantly reversed the inhibition of As₂O₃ and promoted cell migration and angiogenesis in vitro. Further, As₂O₃ significantly inhibited xenograft tumor growth and angiogenesis by upregulating FOXO3a expression in vivo. However, knockdown of FOXO3a attenuated the inhibitory effect of As₂O₃ in xenograft tumors, and increased microvessel density (MVD) and VEGF expression. Our results demonstrated that As₂O₃ inhibited migration and angiogenesis of gastric cancer cells by enhancing FOXO3a expression.

【 授权许可】

Unknown