胃癌无法根治的原因之一是由于胃癌干细胞的存在，目前临床上尚没有满意的清除胃癌干细胞的方法。我们前期研究结果提示：甲硫氨酸应激可以激活胃癌细胞p38蛋白、下调抗氧化酶PRDX6蛋白表达。最新研究发现，干扰能量代谢可以导致干细胞生物学特性改变。为此，我们提出假说：如果能将重组甲硫氨酸酶（rMETase）基因特异性导入胃癌干细胞内并合成有活性的rMETase，就可以在胃癌干细胞内造成甲硫氨酸应激，从而激活p38蛋白阻断mTOR信号通路来抑制糖酵解，同时又能通过增加氧自由基来损伤线粒体功能，达到全面切断胃癌干细胞能量供应的目的，进而杀灭胃癌干细胞。基于此新设想，本项目在前期制备纳米载体的基础上，构建装载rMETase基因的仿生型纳米金给药载体，检测其对胃癌干细胞特异性杀伤作用；同时研究甲硫氨酸应激对胃癌干细胞线粒体和糖酵解两个主要能量代谢途径的影响和调控的机制。所得结果将为胃癌靶向治疗提供新思路。

Elimination or inhibition of gastric cancer stem cells is the key to prevent the recurrence of gastric cancer. At present there is no satisfactory clinical method of removal of gastric cancer stem cell. Our previous study showed that p38 protein is activated and the expression of antioxidase PRDX6 protein is downregulated in gastric cancer cells in methionine stress. The new study find that disturbance of energy metabolism can lead to change of biological characteristics of stem cells. We hypothesize that methionine stress can kill gastric cancer stem cell when methionine enzyme gene may be transducted into gastric cancer stem cells with dynamic METase. As methionine stress may inhibit glycolysis of gastric cancer cells through activating p38 protein. As p38 protein can block the mTOR signaling pathway. At the same time, methionine stress may cut off the sources of energy of gastric cancer stem cells through injurying mitochondria with the oxygen free radical. Based on this new idea , we construct reduction response type gold nanoparticles carried rMETase gene using the layer by layer method. Effect of the non viral delivery carrier specific Killing gastric cancer stem cells is be detected.And then, the change and molecular mechanism of mitochondria and glycolytic of gastric cancer stem cell in methionine stress are studied. The results will provide a new way of targeted therapy of gastric cancer.