Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells

Lee,Eun-Sang; Ko,Kyung-Kon; Joe,Young Ae; Kang,Seok-Gu; Hong,Yong-Kil

doi:10.3892/ol.2010.210

Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells

Authors:
- Eun-Sang Lee
- Kyung-Kon Ko
- Young Ae Joe
- Seok-Gu Kang
- Yong-Kil Hong
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Affiliations: Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea, Department of Neurosurgery, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea, Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 137-701, Korea
Published online on: November 23, 2010 https://doi.org/10.3892/ol.2010.210
Pages: 115-121

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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 O6-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.

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