Notch1 regulates stemness and chemotherapeutic sensitivity of human gli-oma U251 cells
10.3969/j.issn.1000-4718.2015.11.004
- VernacularTitle:Notch1对神经胶质瘤 U251细胞干性及化疗药物敏感性的调节
- Author:
Like ZHANG
;
Na XIAN
;
Ling LIN
;
Yuqing GONG
;
Zhiqiang YE
;
Zhihong ZHENG
- Publication Type:Journal Article
- Keywords:
Glioma U251 cells;
Notch1;
Chemotherapeutic sensitivity
- From:
Chinese Journal of Pathophysiology
2015;(11):1943-1949
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate whether Notch1 changes stemness and chemotherapeutic sensitivity in human glioma U251 cells.METHODS: The lentiviral vectors, which expressed Notch1-shRNA or Notch1 intracellular domain ( NICD) , were transfected into U251 cells .Western blot and immunofluorescence staining were applied to monitor the va-lidity of the cells, down-regulation of Notch1 expression or over-expression of NICD.The proportion of CD133 +cells was analyzed by flow cytometry.The expression of nestin and GFAP was identified by immunofluorescence staining.The forma-tion rate of tumor cell spheres and the implanted tumor growth in SCID mice were observed.MTT assay was performed to e-valuate the chemotherapeutic sensitivity to VM-26 and BCNU of the cells with different treatments.RESULTS:Stemness was significantly enhanced in the cells over-expressing NICD.For example, the proportion of CD133 +cells was increased, the expression of nestin was up-regulated, the expression of GFAP was down-regulated, and the formation rate of tumor cell spheres and implanted tumor growth were increased.The chemotherapeutic sensitivity to VM-26 and BCNU of the cells was decreased.In the cells with Notch1 gene down-regulation by RNAi, the stemness was inhibited and chemotherapeutic sensi-tivity was increased.CONCLUSION:Notch1, which leads to the change of stemness and chemotherapeutic sensitivity in human glioma U251 cells, is likely to be a potential molecular target for treatment of glioma.
