γ-生育三烯酚（γ-T3）是维生素E的主要亚型，主要从棕榈树、大麦、核桃和其他植物中提取。 γ-T3具有抗炎、抗氧化和潜在的恶性肿瘤化学预防作用。 γ-T3对癌症抑制机制的作用尚不完全清楚。本研究旨在探讨γ-T3是否增强胃癌自噬作用及其分子机制。结果表明，γ-T3（0-90μmol/L）可抑制胃癌MKN45细胞和AGS细胞的增殖，并呈剂量依赖性地将细胞周期阻滞在G0/G1期。用γ-T3 (0-45μmol/L)处理的MKN45细胞中自噬增加，特别是在30μmol/L剂量处理24小时时。 3-甲基腺嘌呤预处理可逆转这些影响。此外，γ-T3（30μmol/L）还显着下调MKN45细胞中pGSK-3β（ser9）和β-catenin蛋白的表达，且γ-T3（20μmg/kg b.w.）有效降低MKN45细胞的生长BABL/c 小鼠的异种移植。 GSK-3β 抑制剂 -CHIR-99021 逆转了 GSK-3β/β-Catenin 信号传导和自噬的负调节。我们的研究结果表明，γ-T3 增强 GSK-3β/β-Catenin 信号介导的胃癌细胞自噬，这为 γ-T3 增强自噬在胃癌中的作用提供了新的见解。© 2024 Wiley periodicals LLC。

γ-Tocotrienol (γ-T3) is a major subtype of vitamin E, mainly extracted from palm trees, barley, walnuts, and other plants. γ-T3 has effects on anti-inflammation, anti-oxidation, and potential chemoprevention against malignancies. It is still uncompleted to understand the effect of γ-T3 on the inhibitory mechanism of cancer. This study aimed to investigate whether γ-T3 enhanced autophagy in gastric cancer and the underlying molecular mechanism. The results showed that γ-T3 (0-90 μmol/L) inhibited the proliferation of gastric cancer MKN45 cells and AGS cells, and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Autophagy was increased in MKN45 cells treated with γ-T3 (0-45 μmol/L), especially at a dose of 30 μmol/L for 24 h. These effects were reversed by 3-methyladenine pretreatment. Furthermore, γ-T3 (30 μmol/L) also significantly downregulated the expression of pGSK-3β (ser9) and β-catenin protein in MKN45 cells, and γ-T3 (20 mg/kg b.w.) effectively decreased the growth of MKN45 cell xenografts in BABL/c mice. GSK-3β inhibitor-CHIR-99021 reversed the negative regulation of GSK-3β/β-Catenin signaling and autophagy. Our findings indicated that γ-T3 enhances autophagy in gastric cancer cells mediated by GSK-3β/β-Catenin signaling, which provides new insights into the role of γ-T3 enhancing autophagy in gastric cancer.© 2024 Wiley Periodicals LLC.