3,3'-二吲哚甲烷通过钙池操纵性钙内流/AMPK/内质网应激抑制胃癌细胞增殖的分子机制

我国胃癌高发，膳食营养防治具有重要意义。十字花科蔬菜中的植物化学物3,3'-二吲哚甲烷（DIM）可抑制胃癌细胞增殖，但分子机制未彻底阐明，限制了其应用。我们前期研究发现DIM可调控内质网应激、AMPK通路部分分子的表达，以及钙池操纵性钙内流（SOCE）通路相关的钙离子分布。本项目拟以细胞、裸鼠与胃癌人群组织芯片为研究对象，结合分子生物与可视化模型分析技术，观察DIM对内质网应激、AMPK通路分子表达，对SOCE通路胞膜受体GPCR、TKR，以及胞内分子PLCβ、PLCγ、IP3、IP3R、STIM1、Orai1的表达、移位、相互作用的影响，探讨这些分子在DIM抑制胃癌细胞增殖中的作用；并分析DIM膳食摄入与胃癌细胞增殖相关病理的关联。旨在阐明DIM通过SOCE/AMPK/内质网应激抑制胃癌细胞增殖的分子机制，为DIM防治胃癌提供营养学依据，并为基于膳食植物化学物的肿瘤精准预防确立分子基础。

Gastric cancer is one of the most common types of malignant tumor in China. 3,3'-diindolylmethane (DIM), an active phytochemical derivative extracted from cruciferous vegetables, possesses anticancer effects. However, the underlying anti-cancer mechanism of DIM in gastric cancer remains unknown. Our previous research found that DIM may regulating the AMPK/ER stress pathway and calcium related SOCE. In the present study, CHOP, ATF6, p-AMPK, GPCR, TKR, PLCβ, PLCγ, IP3, IP3R, STIM1, Orai1 after DIM treatment will be investigated in gastric cancer cells, nude mice and tissue microarray. The correlation between DIM intake and gastric cancer was also analyzed. This study aims to elucidate the molecular mechanism of DIM inhibiting gastric cancer cell proliferation through SOCE/AMPK/ER stress, as to offer a novel strategy for the prevention and treatment of gastric cancer.