Reactive Oxygen Species Are Involved in the Development of Gastric Cancer and Gastric Cancer-Related Depression through ABL1-Mediated Inflammation Signaling Pathway

BACKGROUND: The mechanisms of crosstalk between depression and gastric cancer (GC) remain ill defined. Given that reactive oxygen species (ROS) is involved in the pathophysiology of both GC and depression, we try to explore the activities of ROS in the development of GC and GC-related depression.

METHODS: 110 patients with newly diagnosed GC were recruited in our study. The clinical characteristics of these patients were recorded. Inflammation and oxidative stress markers were detected by ELISA. The depression status of patients with GC was assessed during follow-up. The association between ROS, ABL1, and inflammation factors was evaluated in H2O2-treated GC cell lines and The Cancer Genome Atlas (TCGA) database. The effect of ABL1 on inflammation was detected with Imatinib/Nilotinib-treated GC cell lines. A chronic mild stress- (CMS-) induced patient-derived xenograft (PDX) mice model was established to assess the crosstalk between depression and GC.

RESULTS: Depression was correlated with poor prognosis of patients with GC. GC patients with depression were under a high level of oxidative status as well as dysregulated inflammation. In the CMS-induced GC PDX mice model, CMS could facilitate the development of GC. Additionally, tumor bearing could induce depressive-like behaviors of mice. With the treatment of ROS, the activities of ABL1 and inflammatory signaling were enhanced both in vitro and in vivo, and blocking the activities of ABL1 inhibited inflammatory signaling.

CONCLUSIONS: ROS-activated ABL1 mediates inflammation through regulating NF-κB1 and STAT3, which subsequently leads to the development of GC and GC-related depression.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:2019

Enthalten in:

Oxidative medicine and cellular longevity - 2019(2019) vom: 01., Seite 5813985

Sprache:

Englisch

Beteiligte Personen:

Huang, Tianhe [VerfasserIn]
Zhou, Fuling [VerfasserIn]
Yuan, Xiaohan [VerfasserIn]
Yang, Tian [VerfasserIn]
Liang, Xuan [VerfasserIn]
Wang, Yu [VerfasserIn]
Tu, Honglei [VerfasserIn]
Chang, Jiantong [VerfasserIn]
Nan, Kejun [VerfasserIn]
Wei, Yongchang [VerfasserIn]

Links:

Volltext

Themen:

8-Hydroxy-2'-Deoxyguanosine
88847-89-6
8A1O1M485B
Antineoplastic Agents
EC 2.7.10.2
Imatinib Mesylate
Inflammation Mediators
Journal Article
Proto-Oncogene Proteins c-abl
Reactive Oxygen Species

Anmerkungen:

Date Completed 03.01.2020

Date Revised 09.04.2022

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1155/2019/5813985

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM30006926X