Helium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathway

Low temperature plasma (LTP) has emerged as a new research hotspot of promising therapy to fight against cancer. Autophagy is a multifunctional process that digests and recycles cellular contents within lysosomes to maintain homeostasis, which is the underlying mechanism of cancer cell death and ant...

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Main Authors: Y. Wu, J. Liu, L. Gao, Y. Ma, G. Xu, X. Li, Y. Hao, X. Shi, Guan-Jun Zhang
Format: Article
Language:English
Published: AIP Publishing LLC 2019-09-01
Series:AIP Advances
Online Access:http://dx.doi.org/10.1063/1.5116292
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author Y. Wu
J. Liu
L. Gao
Y. Ma
G. Xu
X. Li
Y. Hao
X. Shi
Guan-Jun Zhang
author_facet Y. Wu
J. Liu
L. Gao
Y. Ma
G. Xu
X. Li
Y. Hao
X. Shi
Guan-Jun Zhang
author_sort Y. Wu
collection DOAJ
description Low temperature plasma (LTP) has emerged as a new research hotspot of promising therapy to fight against cancer. Autophagy is a multifunctional process that digests and recycles cellular contents within lysosomes to maintain homeostasis, which is the underlying mechanism of cancer cell death and anti-cancer treatment. This study aimed at investigating whether autophagy of HepG2 cells could be induced by LTP and revealing the related molecular mechanism. For this purpose, the atmospheric pressure plasma jet (APPJ) in helium was utilized to generate plasma-actived medium (PAM) to treat HepG2 cells in vitro. Catalase (CAT), superoxide dismutase (SOD) and 3-methyladenine (3-MA) were respectively added into the PAM as the intervention group. The cell viability, formation of autophagosomes, intracellular reactive oxygen species (ROS) level, expression levels of autophagy-associated proteins and key proteins involved in PI3K/AKT/mTOR pathways were detected. The results showed that LTP inhibited cell viability in a dose- and time-dependent manner. Autophagy was induced through the formation of autophagosomes, conversion of LC3-II/LC3-I, increased expression of beclin 1 and degradation of p62. The mechanism was deduced that LTP enhanced the intracellular ROS level and decreased the phosphorylation level of key proteins in PI3K/AKT/mTOR/p70S6K pathway. However, these effects were blocked by the autophagy inhibitor 3-MA and ROS scavengers (CAT and SOD). The therapeutic efficacy of LTP against HepG2 cells may involve autophagy via suppressing PI3K/AKT/mTOR signaling pathway by LTP-mediated ROS.
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spelling doaj.art-6bedcdcafa10497b8ca49ffafcaf2fbb2022-12-22T01:15:27ZengAIP Publishing LLCAIP Advances2158-32262019-09-0199095034095034-1110.1063/1.5116292053909ADVHelium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathwayY. Wu0J. Liu1L. Gao2Y. Ma3G. Xu4X. Li5Y. Hao6X. Shi7Guan-Jun Zhang8School of Public Health, Medical Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaSchool of Public Health, Medical Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaSchool of Public Health, Medical Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaSchool of Public Health, Medical Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaState Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, ChinaSchool of Nursing, Xi’an Siyuan University, Xi’an, Shaanxi 710038, ChinaSchool of Public Health, Medical Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaSchool of Public Health, Medical Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, ChinaState Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, ChinaLow temperature plasma (LTP) has emerged as a new research hotspot of promising therapy to fight against cancer. Autophagy is a multifunctional process that digests and recycles cellular contents within lysosomes to maintain homeostasis, which is the underlying mechanism of cancer cell death and anti-cancer treatment. This study aimed at investigating whether autophagy of HepG2 cells could be induced by LTP and revealing the related molecular mechanism. For this purpose, the atmospheric pressure plasma jet (APPJ) in helium was utilized to generate plasma-actived medium (PAM) to treat HepG2 cells in vitro. Catalase (CAT), superoxide dismutase (SOD) and 3-methyladenine (3-MA) were respectively added into the PAM as the intervention group. The cell viability, formation of autophagosomes, intracellular reactive oxygen species (ROS) level, expression levels of autophagy-associated proteins and key proteins involved in PI3K/AKT/mTOR pathways were detected. The results showed that LTP inhibited cell viability in a dose- and time-dependent manner. Autophagy was induced through the formation of autophagosomes, conversion of LC3-II/LC3-I, increased expression of beclin 1 and degradation of p62. The mechanism was deduced that LTP enhanced the intracellular ROS level and decreased the phosphorylation level of key proteins in PI3K/AKT/mTOR/p70S6K pathway. However, these effects were blocked by the autophagy inhibitor 3-MA and ROS scavengers (CAT and SOD). The therapeutic efficacy of LTP against HepG2 cells may involve autophagy via suppressing PI3K/AKT/mTOR signaling pathway by LTP-mediated ROS.http://dx.doi.org/10.1063/1.5116292
spellingShingle Y. Wu
J. Liu
L. Gao
Y. Ma
G. Xu
X. Li
Y. Hao
X. Shi
Guan-Jun Zhang
Helium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathway
AIP Advances
title Helium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathway
title_full Helium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathway
title_fullStr Helium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathway
title_full_unstemmed Helium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathway
title_short Helium low temperature plasma induced HepG2 cells autophagy through ROS-mediated PI3K/AKT/mTOR/P70s6k signaling pathway
title_sort helium low temperature plasma induced hepg2 cells autophagy through ros mediated pi3k akt mtor p70s6k signaling pathway
url http://dx.doi.org/10.1063/1.5116292
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