转移性脑肿瘤是中枢神经系统中最常见的恶性肿瘤类型，也是肺癌患者死亡的主要原因之一。本研究旨在评估使用神经干细胞（NSC）编码兔群体酯酶（rCE）和肿瘤坏死因子相关凋亡诱导配体（sTRAIL）的一种新型转移性脑肿瘤伴肺癌治疗的疗效。人胚胎NSC免疫化的HB1.F3中转入了rCE和/或sTRAIL基因。利用ligands和sTRAIL伪受体的表达，评估治疗细胞对人肺癌细胞的细胞毒效应，并在CPT-11的存在下进行了体外实验。编码rCE的人NSC（F3.CE和F3.CE.sTRAIL）在CPT-11的存在下明显抑制了肺癌细胞的生长。将肺癌细胞接种于免疫缺陷小鼠中，通过心脏动脉注射系统移植治疗细胞，然后采用CPT-11进行治疗。在静息状态下，肺癌细胞中DR4表达和NSC中的DcR1表达分别在CPT-11添加后增加到70%和90%。在接受F3.CE.sTRAIL移植和CPT-11治疗的小鼠中，免疫缺陷小鼠的肿瘤体积显著减小。接受F3.sTRAIL和F3.CE加CPT-11治疗以及F3.CE.sTRAIL加CPT-11治疗的小鼠的存活期也显著延长。通过rCE和sTRAIL基因转导的NSC在体内和体外对脑转移性肺癌具有显著的抗癌效果，当rCE/CPT-11和sTRAIL联合应用时，其作用可能协同增强。这种利用具有不同生物效应的两种治疗基因的干细胞研究可适用于临床应用。

A metastatic brain tumor is the most common type of malignancy in the central nervous system, which is one of the leading causes of death in patients with lung cancer. The purpose of this study is to evaluate the efficacy of a novel treatment for metastatic brain tumors with lung cancer using neural stem cells (NSCs), which encode rabbit carboxylesterase (rCE) and the secretion form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). rCE and/or sTRAIL were transduced in immortalized human fetal NSCs, HB1.F3. The cytotoxic effects of the therapeutic cells on human lung cancer cells were evaluated in vitro with the ligands and decoy receptor expression for sTRAIL in the presence of CPT-11. Human NSCs encoding rCE (F3.CE and F3.CE.sTRAIL) significantly inhibited the growth of lung cancer cells in the presence of CPT-11 in vitro. Lung cancer cells were inoculated in immune-deficient mice, and therapeutic cells were transplanted systematically through intracardiac arterial injection and then treated with CPT-11. In resting state, DR4 expression in lung cancer cells and DcR1 in NSCs increased to 70% and 90% after CPT-11 addition, respectively. The volumes of the tumors in immune-deficient mice were reduced significantly in mice with F3.CE.sTRAIL transplantation and CPT-11 treatment. The survival was also significantly prolonged with treatment with F3.sTRAIL and F3.CE plus CPT-11 as well as F3.CE.sTRAIL plus CPT-11. NSCs transduced with rCE and sTRAIL genes showed a significant anti-cancer effect on brain metastatic lung cancer in vivo and in vitro, and the effect may be synergistic when rCE/CPT-11 and sTRAIL are combined. This stem-cell-based study using two therapeutic genes of different biological effects can be translatable to clinical application.