胃癌干细胞是导致胃癌复发、转移及耐药的根源。抑制胃癌干细胞的增殖、诱导胃癌干细胞的死亡是抗肿瘤药物的最终靶点。我们前期研究发现，重组甲硫氨酸酶（rMETase）能抑制胃癌干细胞的自我更新。研究表明rMETase能够影响肿瘤细胞基因的甲基化, 导致基因表达发生改变。因此我们设想：rMETase可能通过去甲基化多靶点调控相关基因的表达来诱导胃癌干细胞自噬性死亡及凋亡。基于此新设想，本项目利用聚酰胺-胺型树状大分子-透明质酸/基因纳米传递系统将rMETase基因运载入胃癌干细胞中并合成有活性的甲硫氨酸酶，诱导甲硫氨酸饥饿后综合运用胃癌移植瘤模型、活体成像、流式细胞术、免疫荧光、生物芯片等技术，从整体与细胞、分子等水平系统探讨甲硫氨酸饥饿通过表观遗传修饰调控PTEN/PI3K/AKt信号通路诱导自噬性死亡以及筛选并验证与自噬相关的microRNA。本研究将为rMETase的临床应用提供理论依据。

Gastric cancer stem cells are the important cause of recurrence, metastasis and drug resistance of gastric cancer. It is the ultimate target of anti-tumor drugs to inhibit the proliferation of gastric cancer stem cells and induce the death of gastric cancer stem cells. Our previous study found that Methionine starvation can inhibit gastric cancer stem cell self-renewal. Methionine starvation could affect the methylation status of the tumor cell gene and changes gene expression, so we hypothesized that methionine starvation may remove gastric cancer stem cells by induce autophagic cell death and apoptosis of gastric cancer stem by regulation of gene expression. Based on this new idea, we prepare new targeted polyamidoamine dendrimer - hyaluronic acid / nano gene delivery system to introduce recombinant methioninase gene to gastric cancer stem cells causing methionine starvation. We explore mechanism.of gastric cancer stem cell death Involving pathway of autophagy/ apoptosis regulation by gastric cancer xenograft model and flow cytometry and immunofluorescence and biochip technology. This study will provide a theoretical basis for methionine starvation combined with chemotherapy drug killing gastric cancer stem cells .