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Electro-hyperthermia inhibits glioma tumorigenicity through the induction of E2F1-mediated apoptosis

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Title
Electro-hyperthermia inhibits glioma tumorigenicity through the induction of E2F1-mediated apoptosis
Author(s)
Cha, J.; Jeon, T.-W.; Lee, C.G.; Oh, S.T.; Yang, H.-B.; Choi, K.-J.; Daekwan Seo; Yun, I.; Baik, I.H.; Park, K.R.; Park, Y.N.; Lee, Y.-H.
Publication Date
2015-11
Journal
INTERNATIONAL JOURNAL OF HYPERTHERMIA, v.31, no.7, pp.784 - 792
Publisher
INFORMA HEALTHCARE
Abstract
Modulated electro-hyperthermia (mEHT), also known as oncothermia, shows remarkable treatment efficacies for various types of tumours, including glioma. The aim of the present study was to investigate the molecular mechanism underlying phenotypic changes in oncothermic cancer cells. Materials and methods: U87-MG and A172 human glioma cells were exposed to mEHT (42 °C/60 min) three times with a 2-day interval and subsequently tested for growth inhibition using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to mEHT, global changes in gene expression were examined using RNA sequencing. For in vivo evaluation of mEHT, we used U87-MG glioma xenografts grown in nude mice. Results: mEHT inhibited glioma cell growth through the strong induction of apoptosis. The transcriptomic analysis of differential gene expression under mEHT showed that the anti-proliferative effects were induced through a subset of molecular alterations, including the up-regulation of E2F1 and CPSF2 and the down-regulation of ADAR and PSAT1. Subsequent Western blotting revealed that mEHT increased the levels of E2F1 and p53 and decreased the level of PARP-1, accelerating apoptotic signalling in glioma cells. mEHT significantly suppressed the growth of human glioma xenografts in nude mice. We also observed that mEHT dramatically reduced the portion of CD133+ glioma stem cell population and suppressed cancer cell migration and sphere formation. Conclusions: These findings suggest that mEHT suppresses glioma cell proliferation and mobility through the induction of E2F1-mediated apoptosis and might be an effective treatment for eradicating brain tumours. © 2015 Taylor and Francis
URI
https://pr.ibs.re.kr/handle/8788114/1834
ISSN
0265-6736
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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