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

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Arsenic trioxide (As₂O₃) is a traditional Chinese medicine with established antitumor effects, particularly in acute promyelocytic leukemia (APL).
• Previous research indicates As₂O₃ regulates cell proliferation and survival in solid tumors.
• The role of As₂O₃ in gastric cancer, specifically concerning cell migration and angiogenesis via FOXO3a, requires further investigation.

Purpose of the Study:

• To investigate the inhibitory effects of As₂O₃ on gastric cancer cell migration and angiogenesis.
• To determine if these effects are mediated by the regulation of FOXO3a expression.
• To explore the underlying molecular mechanisms involving AKT, VEGF, and MMP9.

Main Methods:

• In vitro studies using gastric cancer cell lines to assess viability, migration, and angiogenesis.
• Western blotting and immunofluorescence to analyze protein expression levels (p-AKT, FOXO3a, VEGF, MMP9).
• In vivo xenograft models in mice to evaluate tumor growth, angiogenesis, and related molecular markers.

Main Results:

• As₂O₃ reduced gastric cancer cell viability, migration, and angiogenesis in a dose-dependent manner.
• As₂O₃ downregulated p-AKT and upregulated nuclear FOXO3a, leading to decreased VEGF and MMP9 expression.
• FOXO3a knockdown reversed As₂O₃'s inhibitory effects in vitro and in vivo, while As₂O₃ treatment inhibited xenograft tumor growth and angiogenesis by upregulating FOXO3a.

Conclusions:

• As₂O₃ inhibits gastric cancer cell migration and angiogenesis by enhancing FOXO3a expression.
• The mechanism involves the modulation of the AKT/FOXO3a signaling pathway, impacting downstream targets like VEGF and MMP9.
• As₂O₃ demonstrates therapeutic potential for gastric cancer by targeting cell migration and angiogenesis through FOXO3a activation.