我国是胃癌高发国家，细胞增殖严重紊乱是胃癌的重要特征，但其分子机制远未阐明。课题组在前期实验中敲减DPP3后发现胃癌细胞增殖受挫，ROS显著升高，NRF2的mRNA水平降低，但其蛋白表达量未改变。因铁死亡本质上与ROS蓄积直接相关，遂提出假想：DPP3是促进胃癌发生的关键基因之一，DPP3通过调节NRF2 的胞内位置和活化状态、而非NRF2表达量，来控制胃癌细胞ROS水平，及细胞铁死亡状态，从而驱动胃癌发生。本课题拟从分子、细胞、组织及动物水平多层次明确DPP3在胃癌发生中的作用，探讨DPP3调节胃癌细胞ROS蓄积、铁死亡的机制；揭示DPP3调节NRF2 的胞内位置和活化状态的机理。研究将从本课题组筛选出的DPP3基因与铁死亡的新视角探讨胃癌细胞增殖紊乱的内因。研究结果可成为提高胃癌靶向治疗效率的关键所在，为胃癌的治疗提供崭新思路和充分的数据基础，也为目前放化疗寻找抗耐药方案奠定理论基础。

The morbidity of gastric cancer remains high in China. Serious disorder of cell proliferation is one of the vital features of gastric cancer, but its molecular mechanism remains unidentified entirely. In the preliminary experiments, we found the proliferation of gastric cancer cell was severely depressed when DPP3 had been knocked down, at the same time, ROS increased significantly, the level of mRNA of NRF2 decreased, while the expression of NRF2 was unchanged. Because ferroptosis is essentially related with the accumulation of ROS, we propose the hypothesis that DPP3 is one of the key genes promoting the development of gastric cancer; DPP3 promotes the development of gastric cancer via modulating the cellular translocation and activation, rather than the expression volume of NRF2, subsequently controlling the accumulation of ROS and the ferroptosis. The role of DPP3 in the development of gastric cancer will be illustrated, the mechanism of DPP3 modulating the accumulation of ROS and ferroptosis in the gastric cancer will be explored, and the cause of DPP3 controlling the intracellular translocation and activation of NRF2 will be unveiled from molecular, cellular, tissue, and animal level. The mechanism of disorder of gastric cancer cell proliferation will be discussed from a new angle which concentrate on the newly screened gene (DPP3) and ferroptosis. The results will be the key for improving the efficiency of targeting treatment of gastric cancer. A new thinking way and sufficient data base will be provided, theory foundation will be furnished for searching the anti-drug resistance of radiotherapy or chemotherapy.