PMID- 31755894
OWN - NLM
STAT- MEDLINE
DCOM- 20200923
LR  - 20231020
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 12
DP  - 2019 Dec 20
TI  - Ivermectin induces autophagy-mediated cell death through the AKT/mTOR signaling 
      pathway in glioma cells.
LID - 10.1042/BSR20192489 [doi]
LID - BSR20192489
AB  - Glioma is one of the most common types of primary brain tumors. Ivermectin (IVM), 
      a broad-spectrum antiparasitic drug, has been identified as a novel anticancer 
      agent due to its inhibitory effects on the proliferation of glioma cells in vitro 
      and in vivo. However, the ability of IVM to induce autophagy and its role in 
      glioma cell death remains unclear. The main objective of the present study was to 
      explore autophagy induced by IVM in glioma U251 and C6 cells, and the deep 
      underlying molecular mechanisms. In addition, we examined the effects of 
      autophagy on apoptosis in glioma cells. In the present study, transmission 
      electron microscopy (TEM), immunofluorescence, Western blot and 
      immunohistochemistry were used to evaluate autophagy activated by IVM. Cell 
      viability was measured by 3-(4,5-dimethylthiazol2-yl)-2, 5-diphenyltetrazolium 
      bromide (MTT) and colony formation assay. The apoptosis rate was detected by flow 
      cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling 
      (TUNEL). Meanwhile, autophagy inhibition was achieved by using chloroquine (CQ). 
      U251-derived xenografts were established for examination of IVM-induced autophagy 
      on glioma in vivo. Taken together, the results of the present study showed that 
      autophagy induced by IVM has a protective effect on cell apoptosis in vitro and 
      in vivo. Mechanistically, IVM induced autophagy through AKT/mTOR signaling and 
      induced energy impairment. Our findings show that IVM is a promising anticancer 
      agent and may be a potential effective treatment for glioma cancers.
CI  - (c) 2019 The Author(s).
FAU - Liu, Jingjing
AU  - Liu J
AD  - School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, 
      China.
FAU - Liang, Hongsheng
AU  - Liang H
AD  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
FAU - Chen, Chen
AU  - Chen C
AD  - School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, 
      China.
FAU - Wang, Xiaoxing
AU  - Wang X
AD  - School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, 
      China.
FAU - Qu, Faling
AU  - Qu F
AD  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
FAU - Wang, Haiyang
AU  - Wang H
AD  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
FAU - Yang, Kongbin
AU  - Yang K
AD  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
FAU - Wang, Qing
AU  - Wang Q
AD  - School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, 
      China.
FAU - Zhao, Ning
AU  - Zhao N
AD  - School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, 
      China.
FAU - Meng, Jing
AU  - Meng J
AD  - School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, 
      China.
FAU - Gao, Aili
AU  - Gao A
AD  - School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 70288-86-7 (Ivermectin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagic Cell Death/*drug effects
MH  - Cell Line, Tumor
MH  - *Glioma/drug therapy/metabolism/pathology
MH  - Humans
MH  - Ivermectin/*pharmacology
MH  - Mice
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC6900471
OTO - NOTNLM
OT  - AKT/mTOR
OT  - Glioma
OT  - Ivermectin
OT  - apoptosis
OT  - autophagy
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/11/23 06:00
MHDA- 2020/09/24 06:00
PMCR- 2019/12/06
CRDT- 2019/11/23 06:00
PHST- 2019/07/25 00:00 [received]
PHST- 2019/11/08 00:00 [revised]
PHST- 2019/11/18 00:00 [accepted]
PHST- 2019/11/23 06:00 [pubmed]
PHST- 2020/09/24 06:00 [medline]
PHST- 2019/11/23 06:00 [entrez]
PHST- 2019/12/06 00:00 [pmc-release]
AID - 221237 [pii]
AID - BSR20192489 [pii]
AID - 10.1042/BSR20192489 [doi]
PST - ppublish
SO  - Biosci Rep. 2019 Dec 20;39(12):BSR20192489. doi: 10.1042/BSR20192489.