Open AccessInhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells
Author(s) -
Eun Sang Lee,
Kyung Kon Ko,
Yeonsoo Joe,
SeokGu Kang,
Yong Kil Hong
Publication year - 2010
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2010.210
Subject(s) - temozolomide , glioma , cancer research , oncogene , stat3 , cell cycle , drug resistance , small interfering rna , apoptosis , biology , viability assay , cell culture , transfection , microbiology and biotechnology , biochemistry , genetics
The alkylating agent temozolomide (TMZ) is an effective drug used for the treatment of malignant gliomas. However, tumor relapse combined with the development of drug resistance remains a significant problem. To clarify the mechanism of the resistance of glioma cells to TMZ chemotherapy, TMZ-resistant glioma cell lines (TR cells) were generated using U373 and U251 human glioma cells, and TMZ-resistance was confirmed via viability and apoptosis assays. The TMZ-resistance of TR cells was not associated with the TMZ-resistance molecule O(6)-methylguanine-DNA-methyltransferase. Notably, the expression level of signal transducers and activators of transcription 3 (STAT3) and serine 727-phosphorylated STAT3 (pSTAT3-Ser727) was highly increased in TR cells, while that of 705-phosphorylated STAT3 (pSTAT3-Tyr705) was decreased. The inhibition of STAT3 expression by small interfering RNA enhanced TR cell TMZ sensitivity. These results suggest that STAT3 contributes to TMZ-resistance in gliomas and is a potential target for the reversal of TMZ-resistance in patients with a recurrent glioma.