An Jing, Yan Hanqi, Li Xingxing, Tan Ruolan, Chen Xinlin, Zhang Zhichao, Liu Yingfei, Zhang Pengbo, Lu Haixia, Liu Yong
Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R.China.
Department of Human Anatomy and Histoembriology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R.China.
Oncotarget. 2017 Aug 14;8(44):76949-76960. doi: 10.18632/oncotarget.20270. eCollection 2017 Sep 29.
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 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 , 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.
肿瘤细胞的侵袭性和浸润性导致胶质瘤预后不良。目前，人们仍迫切需要能够在不损伤正常脑组织的情况下消除肿瘤细胞的新型治疗手段。基于干细胞的治疗已受到广泛关注，神经干细胞（NSC）被认为是靶向治疗基因的有效递送载体之一。然而，神经干细胞是否能直接影响胶质瘤细胞仍有待观察。在本研究中，将大鼠和人类胶质瘤细胞（C6和U251）直接或间接与正常大鼠胚胎神经干细胞共培养。我们发现，在共培养体系中，胶质瘤细胞的存活、增殖、侵袭和迁移均受到显著抑制，而其分化未受影响。在裸鼠中，虽然皮下注射神经干细胞的U251细胞在肿瘤生长方面未观察到显著差异，但荷瘤小鼠的生存状态和生存时间得到了显著改善。与胶质瘤细胞生长受抑制相一致，突变型p53的表达以及AKT、ERK1/2的磷酸化水平降低，而caspase-3的水平显著升高。我们的结果表明，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的抗胶质瘤特性。它可能是一种非常有前景的胶质瘤治疗候选方法。
