International Peace Maternity and Child Health Hospital, School of Medicine , Shanghai JiaoTong University , 910 Hengshan Road , Shanghai 200030 , P. R. China.
Department of General Surgery , The First Affiliated Hospital of University of Science and Technology , 17 LuJiang Road , LuYang District, HeFei 230031 , P. R. China.
J Agric Food Chem. 2019 Jan 9;67(1):441-451. doi: 10.1021/acs.jafc.8b05832. Epub 2018 Dec 27.
γ-Tocotrienol (γ-T3) exhibits the activity of anticancer via regulating cell signaling pathways. Nuclear factor-κB (NF-κB), one of the crucial pro-inflammatory factors, is involved in the regulation of cell proliferation, apoptosis, invasion, and migration of tumor. In the present study, NF-κB activity inhibited by γ-T3 was investigated in gastric cancer cells. Cell proliferation, NF-κB activity, active protein phosphatase type 2A (PP2A), and ataxia-telangiectasia mutated (ATM) protein were explored using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT), methylene blue, enzyme-linked immunosorbent assay (ELISA), malachite green, luciferase, and Western blotting assays. The effects of γ-T3 on tumor growth and the expression of NF-κB and PP2A proteins were also further examined by implanting human gastric cancer cells in a BALB/c nude mouse model. The results showed that γ-T3 significantly inhibited the cell proliferation and attenuated the NF-κB activity in vitro and in vivo. γ-T3 dramatically increased PP2A activity and protein expression, which suppressed ATM phosphorylation and its translocation to the cytoplasm in gastric cancer cells. Thus, our findings may provide mechanistic insight into effects of γ-T3 on the regulation of NF-κB activity by a PP2A-dependent mechanism and suggest that PP2A may serve as a molecular target for a potential chemopreventive agent.
γ-生育三烯酚（γ-T3）通过调节细胞信号通路表现出抗癌活性。核因子-κB（NF-κB）是关键的促炎因子之一，参与肿瘤细胞的增殖、凋亡、侵袭和迁移的调节。在本研究中，研究了 γ-T3 对胃癌细胞中 NF-κB 活性的抑制作用。使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐（MTT）、亚甲蓝、酶联免疫吸附测定（ELISA）、孔雀绿、荧光素酶和 Western blot 测定法研究了细胞增殖、NF-κB 活性、活性蛋白磷酸酶 2A（PP2A）和共济失调毛细血管扩张突变（ATM）蛋白。还通过将人胃癌细胞植入 BALB/c 裸鼠模型进一步研究了 γ-T3 对肿瘤生长和 NF-κB 和 PP2A 蛋白表达的影响。结果表明，γ-T3 显著抑制细胞增殖，并在体外和体内减弱 NF-κB 活性。γ-T3 显著增加了 PP2A 活性和蛋白表达，抑制了 ATM 磷酸化及其向细胞质的易位。因此，我们的发现可能为 γ-T3 通过 PP2A 依赖性机制调节 NF-κB 活性的作用提供机制上的见解，并表明 PP2A 可能作为潜在化学预防剂的分子靶标。
