Inhibition of EZH2 reverses chemotherapeutic drug TMZ chemosensitivity in glioblastoma.
Int J Clin Exp Pathol
; 7(10): 6662-70, 2014.
Article
in En
| MEDLINE
| ID: mdl-25400745
ABSTRACT
Glioblastoma remains among the most devastating cancers with a median survival of less than 15 months and virtually no survival beyond five years. Currently, the treatment of glioma includes surgery, radiation therapy, chemotherapy, and comprehensive treatment. Intrinsic or acquired resistance to TMZ, is one of the greatest obstacles in successful GB treatment, and is thought to be influenced by a variety of mechanisms. The EZH2 gene, which is expressed in various solid tumors, can regulate gene transcription and promote the generation and progression of tumors. Our aim was to investigate the relationship between EZH2 and multidrug-resistance of human glioblastoma cells. In this study, we established TMZ-resistant U251 and U87 clones (U251/TMZ and U87/TMZ cells), which expressed high level of EZH2. Using RNA interference, we demonstrated that the downregulation of Ezh2 expression in U251/TMZ and U87/TMZ cells resulted in apoptosis and a cell cycle arrest in the G1/S phase. Furthermore, the reduced expression of Ezh2 altered the MDR, MRP and BCRP mRNA and protein levels. These findings suggest that EZH2 plays an important part in the development of multidrug resistance and may represent a novel therapeutic target for multidrug-resistant glioblastoma.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioblastoma
/
Drug Resistance, Neoplasm
/
Antineoplastic Agents, Alkylating
/
Dacarbazine
/
Polycomb Repressive Complex 2
Limits:
Humans
Language:
En
Journal:
Int J Clin Exp Pathol
Journal subject:
PATOLOGIA
Year:
2014
Document type:
Article