@article{oai:repo.qst.go.jp:00077677,
 author = {Ho Kim, Eun and Jo, Yunhui and Sai, Sei and Mung-Jin, Park and Jeong-Yub, Kim and Su Kim, Jin and Yeon-Joo, Lee and Jae-Min, Cho and Seo-Young, Kwak and Jeong-Hwa, Baek and Kyoung Jeong, Youn and Jie-Young, Song and Yoon, Myonggeun and Sang-Gu, Hwang and Ho Kim, Eun and Sei, Sai},
 issue = {39},
 journal = {Oncogene},
 month = {Jan},
 note = {Tumor-treating fields (TTFs) - a type of electromagnetic field-based therapy using low-intensity electrical fields - has recently been characterized as a potential anticancer therapy for glioblastoma multiforme (GBM). However, the molecular mechanisms involved remain poorly understood. Our results show that the activation of autophagy contributes to the TTF-induced anti-GBM activity in vitro or in vivo and GBM patient stem cells or primary in vivo culture systems. TTF-treatment upregulated several autophagy-related genes (~2-fold) and induced cytomorphological changes. TTF-induced autophagy in GBM was associated with decreased Akt2 expression, not Akt1 or Akt3, via the mTOR/p70S6K pathway. An Affymetrix GeneChip miRNA 4.0 Array analysis revealed that TTFs altered the expression of many microRNAs (miRNAs). TTF-induced autophagy upregulated miR-29b, which subsequently suppressed the Akt signaling pathway. A luciferase reporter assay confirmed that TTFs induced miR-29b to target Akt2, negatively affecting Akt2 expression thereby triggering autophagy. TTF-induced autophagy suppressed tumor growth in GBM mouse models subjected to TTFs as determined by positron emission tomography and computed tomography (PET-CT). GBM patient stem cells and a primary in vivo culture system with high Akt2 levels also showed TTF-induced inhibition. Taken together, our results identified autophagy as a critical cell death pathway triggered by TTFs in GBM and indicate that TTF is a potential treatment option for GBM.},
 pages = {6630--6646},
 title = {Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells},
 volume = {38},
 year = {2019}
}