大鼠神经干细胞通过Wnt/β-catenin途径抑制神经胶质瘤生长

Objective To study the effect of rat neural stem cells on C6 glioma cell proliferation and to explore the possible mechanism. Methods We co-cultured neural stem cells with C6 glioma cells at different ratios (1:1[2×10^5:2×10^5], 1:5[4×10^4:2×10^5], 5:1 [2×10^5:4×10^4]) 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). Results Compared 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). Conclusion Rat neural stem cells may inhibit the tumorigenicity of C6 glioma cells by promoting apoptosis through Wnt/β-catenin pathway.