CCND1 silencing promotes chemosensitivity of glioblastoma cell lines to temozolomide
10.16781/j.0258-879x.2017.12.1503
- Author:
Wei ZHAO
1
Author Information
1. Department of Neurosurgery, Changzheng Hospital, Institute of Shanghai Neurosurgical Research, Second Military Medical University
- Publication Type:Journal Article
- Keywords:
Cyclin D1 gene;
Glioblastoma;
Multiple drug resistance;
Temozolomide
- From:
Academic Journal of Second Military Medical University
2017;38(12):1503-1507
- CountryChina
- Language:Chinese
-
Abstract:
Objective To screen chemotherapeutic drugs that can synergistically inhibit the proliferation of glioblastoma cells with CCND1 by constructing CCND1-silenced and overexpressed human glioblastoma cell lines SHG-44. Methods SHG-44 cells with CCND1 silenced or overexpressed were constructed, and the expression of P-glycoprotein (P-gp, expression product of multidrug resistance geneMDR1) and apoptotic factors CBcl-2, Caspase-3) in the cells were detected by Western blotting. The SHG-44 cells with CCND1 silenced or overexpressedwere cultured with carmustine GBCNU), lomustine (CCNU) and temozolomide (TMZ), respectively; and then the available chemotherapeutic drugs were screened, which could synergistically inhibit the proliferation of tumor cells with CCND1 sliencing. Human glioblastoma cell lines U251 were used toverify the findings in SHG-44cells. Results Western blotting analysis showed that CCND1 silencing significantly down-regulated the expressions of MDR1 and Bcl-2, and up-regulated the expression of Caspase-3 (all P<0. 01). There were no significant differences in cell growth curves between the CCND1-silenced cells treating with BCNU (0. 05 µg/mL, 0. 25 µg/mL) and CCNU (20 µg/mL, 80 µg/mL) for 2, 3, 4, and 5 days; However, the proliferation of CCNDUsilenced SHG-44 cells was significantly inhibited by TMZ (9. 1 µg/mL) compared with parent SHG-44 cells on the 4th and 5th day after treatment (P<0. 05). The findings that CCND1 silencing promoted chemosensitivity of TMZ were confirmed by U251 cellexperiments. Conclusion CCND1 silencing combined with TMZ is more effective in inhibiting the proliferation of human glioblastoma cell lines SHG-44 than CCND1 silencing or TMZ alone, suggesting that CCND1 may be involved in chemotherapeutic resistance of glioblastoma cells to TMZ.
