The inhibiting effect of neural stem cells on proliferation and invasion of glioma cells.

The inhibiting effect of neural stem cells on proliferation and invasion of glioma cells.
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神经干细胞对胶质瘤细胞增殖和侵袭的抑制作用

DOI:
10.18632/oncotarget.20270
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发表时间:
2017-09-29
期刊:
影响因子:
--
通讯作者:
Liu Y
Liu Y
中科院分区:
其他
文献类型:
--
作者:
An J;Yan H;Li X;Tan R;Chen X;Zhang Z;Liu Y;Zhang P;Lu H;Liu Y

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肿瘤细胞的侵袭性和浸润性导致胶质瘤预后不良。目前,仍然强烈需要在不损害正常脑组织的情况下消除肿瘤细胞的新的治疗手段。基于干细胞的基因治疗受到了广泛关注,神经干细胞被认为是靶向治疗基因的有效载体之一。然而,神经干细胞是否可以直接影响胶质瘤细胞仍有待观察。本研究将大鼠和人胶质瘤细胞(C6和U251)与正常大鼠胚胎神经干细胞直接或间接共培养。结果发现,在体外共培养体系中,胶质瘤细胞的存活、增殖、侵袭和迁移能力受到明显抑制,而分化能力不受影响。在裸小鼠中,虽然肿瘤生长没有观察到明显差异,但皮下注射神经干细胞后,荷瘤小鼠的生存状态和生存时间明显提高。在体外抑制胶质瘤细胞生长的同时,突变型p53表达和AKT、ERK 1/2磷酸化水平显著降低,caspase-3水平显著升高。结果提示,正常神经干细胞可通过抑制胶质瘤细胞的活力、增殖、侵袭和迁移而具有直接抗胶质瘤的作用。它可能是一个非常有前途的候选神经胶质瘤治疗。
The invasive and infiltrative nature of tumor cells leads to the poor prognosis of glioma. Currently, novel therapeutic means to eliminate the tumor cells without damaging the normal brain tissue are still strongly demanded. Significant attentions had been paid to stem cell-based therapy and neural stem cell (NSC) had been considered as one of the efficient delivery vehicles for targeting therapeutic genes. However, whether the NSCs could directly affect glioma cells remains to be seen. In this study, both rat and human glioma cells (C6 and U251) were co-cultured with normal rat embryonic NSCs directly or in-directly. We found the survival, proliferation, invasion and migration of glioma cells were significantly inhibited, while the differentiation was not affected in the in vitro co-culture system. In nude mice, although no significant difference was observed in the tumor growth, survival status and time of tumor-bearing mice were significantly promoted when U251 cells were subcutaneously injected with NSCs. In coincidence with the suppression of glioma cell growth in vitro, expression of mutant p53 and phosphorylation of AKT, ERK1/2 decreased while the level of caspase-3 increased significantly. Our results suggested that normal NSCs could possess direct anti-glioma properties via inhibiting the glioma cell viability, proliferation, invasion and migration. It could be a very promising candidate for glioma treatment.
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