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작성일 : 20-03-09 18:01
Tumor-treating fields induce autophagy by blocking the Akt2/ miR29b axis in glioblastoma cells
 글쓴이 : 관리자
조회 : 3,767  

  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 TTFinduced 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). TTFinduced
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.

Eun Ho Kim, Yunhui Jo1,2 , Sei Sai3 , Mung-Jin Park1 , Jeong-Yub Kim1, Jin Su Kim4, Yeon-Joo Lee 1,
Jae-Min Cho1, Seo-Young Kwak5, Jeong-Hwa Baek1, Youn Kyoung Jeong6, Jie-Young Song 1,
Myonggeun Yoon2, Sang-Gu Hwang1

Oncogene (2019) 38:6630–6646