title: Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells.
abstract: 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.
authors.affiliation: Cancer Research Institute, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Eun-Sang
authors.initials: ES
authors.lastname: Lee
authors.forename: Kyung-Kon
authors.initials: KK
authors.lastname: Ko
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Joe
authors.forename: Seok-Gu
authors.initials: SG
authors.lastname: Kang
authors.forename: Yong-Kil
authors.initials: YK
authors.lastname: Hong