| 摘要: |
| \[摘要\]目的探讨大鼠神经干细胞对C6成胶质细胞瘤细胞生长的影响,并探讨可能的作用机制。方法采用0.4 μm孔径的Transwell小室将C6成胶质细胞瘤细胞和大鼠神经干细胞(NSCs)按不同比例\[(C6NSCs):51(2×1054×104)、11(2×1052×105)、15(4×1042×105)\]在无血清培养基中共培养7 d作为实验组,以单独培养的C6成胶质细胞瘤细胞作为对照组。采用SCID荷瘤动物模型观察共培养体系中C6成胶质细胞瘤细胞的成瘤能力；利用半定量RT-PCR及蛋白质印迹等方法分析在共培养体系中C6成胶质细胞瘤细胞凋亡相关基因(BMP2、c-Myc、Bcl-2、p53 mRNA)及Wnt信号分子蛋白(β-catenin、survivin)的表达。结果与实验组相比,对照组的组织切片中肿瘤细胞恶性程度高,有较多的核分裂像,核/质比例高;大片区域出现单核或多核瘤巨细胞。在实验组中,随着共培养体系中起始神经干细胞比例增高,肿瘤细胞异型性逐步降低。随着共培养体系中起始神经干细胞比例增高,C6成胶质细胞瘤细胞p53 mRNA的表达水平逐步增高,BMP2、c-Myc、Bcl-2 mRNA表达水平则逐步降低(P<0.05)，β-catenin、survivin蛋白表达水平逐步降低(P<0.05)。结论大鼠神经干细胞在胶质瘤微环境中可能通过Wnt/β-catenin途径促进神经胶质瘤细胞凋亡进而抑制神经胶质瘤生长。 |
| 关键词: 神经干细胞；胶质母细胞瘤 Wnt/β-catenin信号转导通路；细胞凋亡 |
| DOI：10.3724/SP.J.1008.2010.01277 |
| 投稿时间：2010-06-23修订日期：2010-11-10 |
| 基金项目:国家高技术研究发展计划(“863”计划,2005AA001070). |
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| Rat neural stem cells inhibit C6 glioma cell proliferation through Wnt/β-catenin pathway |
| LI Yi-ming1, LI Wei-qing2, LU Yi-cheng1*, YU Hong-yu2, HAN Huan-xing3, HE Jin2, XU Yi2 |
| (1. Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; 2. Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; 3. Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China) |
| Abstract: |
| \[Abstract\]ObjectiveTo study the effect of rat neural stem cells on C6 glioma cell proliferation and to explore the possible mechanism.MethodsWe co-cultured neural stem cells with C6 glioma cells at different ratios (11\[2×105 2×105\], 15\[4×1042×105\],51 \[2×1054×104\]) in serum-free medium using Transwell chamber culture system for 7 days, and C6 glioma cells cultured alone served as controls. The tumorigenic ability of C6 glioma cells was observed by means of SCID mice transplantation. RT-PCR and Western blotting analysis were used to examine the expression of apoptosis-related proteins (BMP2, c-Myc, Bcl-2 and p53 mRNA) and Wnt signal molecules (β-catenin and survivin).ResultsCompared with the experimental group, the tumor cells in the tissue section of the control group had a higher malignant degree, with more mitoses, higher nuclear/cytoplasm ratio, and there were abundant single- or multi-core giant tumor cells in the tissue section. With the increase of neural stem cell proportion in the co-culture system, the tumor cell atypia degree decreased gradually, the expression of p53 mRNA in C6 glioma cells increased gradually, the expression of bone morphogenetic protein 2, Bcl-2, and c-Myc mRNA was decreased significantly (P<0.05), and the expression of β-catenin, survivin protein was decreased significantly(P<0.05). ConclusionRat neural stem cells may inhibit the tumorigenicity of C6 glioma cells by promoting apoptosis through Wnt/β-catenin pathway. |
| Key words: neural stem cells glioblastoma Wnt/β-catenin transduction pathway apoptosis |
