膜结合型前列腺素E2合酶 1（mPGES-1），是前列腺素E2（PGE2）生物合成的终端限速酶。最近的研究发现mPGES-1高表达于多种实体瘤细胞及组织中，可望成为肿瘤治疗的靶基因。在前期实验中，我们率先报道急性白血病（AL）细胞株及原代细胞均高表达mPGES-1，抑制mPEGS-1表达可下调PGE2合成，显著诱导AL细胞凋亡。本课题组拟在前期研究基础上，以RNA干扰技术特异性抑制mPGES-1表达，通过体外实验观察mPGES-1基因沉默对AL细胞株增殖、凋亡、侵袭及药物敏感性的影响，检测NF-κB信号网络、VEGF、基质金属蛋白酶MMP2、MMP9等因子的变化。并建立人白血病-NOD/SCID小鼠移植模型，通过动物实验观察mPGES-1基因沉默后AL细胞生物学行为的变化。希望从多角度探讨mPGES-1在AL发生、发展中的作用，从而为以mPGES-I为新靶点的AL基因治疗研究提供实验依据。

Membrane-bound prostaglandin E2 synthase 1 (mPGES-1)，the terminal enzyme for specific modulation of PGE2 production, has been recently reported to be expressed at high levels in a variety of solid tumor cells and tissues and may present a potential target gene for cancer therapy.Our earlier study revealed, for the first time，that mPGES-1 is over-expressed in both human acute leukemia (AL) cell lines and primary cells. As a result of down-regulation of mPGES-1 expression and PGE2 synthesis, AL cells were markedly induced apoptosis. Base on the preliminary results, we will design and synthesize a pair of siRNA based on mPGES-1 sequence in AL cells to specifically down-regulate the expression of mPGES-1. The effects of mPGES-1 gene silence on proliferation, apoptosis, invasion and drug sensitivity of AL cells and NF-κB signal network, VEGF, and MMP2, MMP9 expression will be investigated as well.Furthermore, a NOD/SCID murine model of human leukemia will be establishedd to observe the effect of mPGES-1 siRNA on leukemia cells biological behavior in vivo. Through multiple perspectives, our study expects to clarify the effects of mPGES-1 on leukemogenesis and its mechanism, and provide some experimental basis to consider mPGES-1 as a new therapeutic gene target for AL．