学者简介以及论文摘要
陈沉博士:
2017年毕业于青岛大学公共卫生学院,营养与食品卫生专业,获得医学博士学位,现于青岛大学基础学院博士后流动站工作。2010年~2017年来一直从事植酸抗结直肠癌研究相关工作,对植酸抗结直肠癌的作用及其相关机制有着深入的认识和研究。参与国家自然基金”肌醇六磷酸及其次级磷酸化形式对结直肠癌发病和肠道菌群的影响”项目,发表关于植酸抗结直肠癌文章5篇,其中第一作者身份在SCI收录期刊发表论文一篇。
Inositol hexaphosphate hydrolysate competitively binds to AKT to inhibit the proliferation of colon carcinoma.
Phytate, myto-inositol 1,2,3,4,5,6 hexaphosphate (IP6), is recognized as an anti-nutrition phytochemical for decades. Recently, numerous studies have indicated that IP6 and its hydrolysates could suppress colon oncogenesis. However, very little is known concerning the mechanism of IP6 hydrolysates in regulating colon oncogenesis. The aim of the present study was to identify the underlying relationship between IP6 hydrolysates and colon cancer. Three types of human colorectal cancer cells were utilized in the present study. The proliferationinhibition and migration assays were employed to reveal that IP6 hydrolysates inhibited the proliferation of SW620 cells. Real-time PCR, cell-based ELISA and the AKT inhibitor assay were utilized to reveal that 20 and 30% degree of hydrolysis hydrolysates of IP6 inhibited SW620 cell growth by inhibiting the activation of AKT protein. The docking simulation study revealed that IP4 and IP5 could inhibit the activation of AKT by binding to PIP3 receptor. Collectively, our results indicated that the IP6 hydrolysates inhibit SW620 cell proliferation; IP4 and IP5, the probable primary constituents of the 20-30% degree of hydrolysis hydrolysates of IP6, inhibited the proliferation of SW620 cells by competitively inhibiting the AKT protein.
六磷酸肌醇水解物竞相与蛋白激酶(AKT)的结合,有效抑制结肠癌的扩散繁殖。
植酸、肌-肌醇六磷酸1,2,3,4,5,6(IP6),几十年来被公认为一种抗营养植物素。近年来,许多研究都表明,六磷酸肌醇(IP6)及其水解产物能抑制结肠癌的发生。然而,很少有人知道IP6水解物对结肠肿瘤具有调节作用的原理。本课题的目的是确定六磷酸肌醇(IP6)水解物与结肠癌之间的潜在关系,对三种类型的人结肠癌细胞进行了研究。扩散抑制和迁移说测定分析表明,六磷酸肌醇(IP6)水解物抑制了人结肠癌细胞(SW620)的增殖。实时定量聚合酶链反应PCR,基于细胞的酶联免疫吸附试验ELISA和蛋白激酶Akt抑制剂法显示20%和30%程度的六磷酸肌醇(IP6)水解作用酶解液通过阻断蛋白激酶(AKT)的活化抑制人结肠癌细胞(SW620)的生长。对接模拟研究显示,IP4 IP5能够通过与结构域与位于质膜的磷脂酰肌醇三磷酸(PIP3)的受体结合来抑制蛋白激酶的活化。总的来说,我们的研究结果表明,六磷酸肌醇(IP6)水解物抑制人结肠癌细胞(SW620)的增殖;IP4和IP5,极大可能主要是20-30%程度的六磷酸肌醇(IP6)水解物,竞相阻断蛋白激酶(AKT)从而抑制人结肠癌细胞(SW620)的增殖。