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

Abstract

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.

Post-surgery anxiety and depression in prostate cancer patients: prevalence, longitudinal progression, and their correlations with survival profiles during a 3-year follow-up

“…A study elucidates that depression plays a role in enhancing the progression of hepatocellular carcinoma in mice via increasing programmed death 1 (PD-1) level regulated by glucocorticoids in tumor infiltrating natural killer (NK) cells [24]. Another study reveals that depression correlates with worse clinical outcome in gastric cancer patients, and the in vivo and in vitro experiments disclose that gastric cancer-related depression involves the participation of reactive oxygen species via the ABL1-modulated inflammatory pathway [25]. In addition, a previous study illustrates that anxiety and depression play a role in mediating the correlation of chemotherapy-induced peripheral neuropathy with fatigue in colorectal cancer patients; however, this study also states that this needs more experimental evidence to validate [26].…”

“…Second, anxiety and depression also induce many physical symptoms, such as fatigue, insomnia, and change of weight as well as appetite; these all contribute to a worse physical function and may interfere with the physical health of prostate cancer patients [31,32]. Third, anxiety and depression may aggregate the disease in prostate cancer patients via affecting several biological processes or pathways, such as regulating the tumor infiltrating NK cells and reactive oxygen species [24][25][26][27]. In the future, the status of anxiety and depression may be useful in optimizing the prognosis prediction in surgical prostate cancer patients; however, this should be validated by more highquality trials or large-scale cohort studies.…”

Application of Animal Models in Cancer Research: Recent Progress and Future Prospects

“… [ 166 ] Gastric cancer Mouse ROS-activated ABL1 mediates inflammation through regulating NF-κB1 and STAT3, which subsequently leads to the development of GC and GC-related depression. [ 167 ] Gastric cancer Mouse Gastrin inhibited GC growth and enhanced the suppression of GC by cisplatin in mice or PGC cell culture models through activating the ERK-P65-miR23a/27a/24 axis or its components. [ 168 ] Gastric cancer Mouse LH inhibited tumorigenicity in gastric cancer through down-regulating the expression of MCL1.…”

Aerobic Exercise Inhibits CUMS-Depressed Mice Hippocampal Inflammatory Response via Activating Hippocampal miR-223/TLR4/MyD88-NF-κB Pathway

“…Recently, studies have shown that the pathogenesis of hippocampal lesions and neuronal cell death in patients with depression might be related to the explosive activation of inflammatory reactions [1]. The "cytokine theory" suggests that stress-stimulated or over-activated immune systems produce inflammatory cytokines and play an important role in the pathogenesis of depression [2], which have been confirmed by clinical trials [3][4][5] and animal experiments [6,7]. Therefore, anti-inflammatory treatment for reducing the hippocampal inflammatory response and improving hippocampal function have become a new target for the prevention and treatment of depression.…”