Effect of Curcumin on Gene Expression of Trx/TxrR System and PI3K/Akt/mTOR Signaling Pathway in SKOV3 Cells Resistant to Cisplatin

2020 ◽  
Vol 159 ◽  
pp. S55
Author(s):  
Elena Kalinina ◽  
Aseel Ali Hasan ◽  
Albina Petrova ◽  
Maria Novichkova ◽  
Dmitry Zhdanov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Skov3 Cells

scholarly journals Apolipoprotein C-II induces EMT to Promote Gastric Cancer Peritoneal Metastasis via PI3K/AKT/mTOR Pathway

2021 ◽  
Author(s):  
Chao Wang ◽  
Zhi Yang ◽  
En Xu ◽  
Xingzhou Wang ◽  
Zijian Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Peritoneal Metastasis ◽  
Mtor Signaling ◽  
Tandem Mass ◽  
Mtor Signaling Pathway ◽  
Apolipoprotein C

Abstract Background: Peritoneal metastasis (PM) occurs frequently in patients with gastric cancer (GC) and confers poor survival. Lipid metabolism and epithelial-mesenchymal transition (EMT) play an important role in GC metastasis. As Apolipoprotein C-II (APOC2) is a key protein in lipid metabolism, few studies have investigated the role of APOC2 in PM. This study aims to elucidate the potential molecular mechanism of APOC2 in the PM of GC.Methods: The Tandem Mass Tagging (TMT) method followed by liquid chromatography-tandem mass spectrometry-based proteomics analysis was used to compare the levels of differentially expressed proteins between human PM and GC tissues. APOC2 expression was evaluated by immunoblotting, and immunohistochemistry analysis (n = 111). APOC2 over-expression and knock-down expression cell models were developed and tested in vitro. RNA sequencing analysis evaluated the changes in gene expression after APOC2 knockdown in GC cells. The Agilent Seahorse XF platform and lipid staining assay were used to evaluate the role of APOC2 in lipid metabolism of GC cells. Spheroid cell invasion assay, apoptosis assay, colony formation assay, wound-healing assays, and transwell assays were performed and peritoneal implants into nude mice were done to assess the biological effects of APOC2. The underlying mechanisms were investigated using Western blot, inhibitor or activator treatment assays.Results: APOC2 was highly abundant in GC cells and PM tissues. And high APOC2 levels in GC tissues correlated with poor patient prognosis. Knockdown of APOC2 inhibited the malignant phenotype of cancer cells and EMT significantly. Massive gene expression alterations after APOC2 knockdown, which were associated with various signaling pathways, especially the PI3K/AKT signaling pathway and lipid metabolism. Furthermore, the regulatory effects of APOC2 on the EMT were partially attributed to the PI3K/AKT/mTOR signaling pathway. The results in vivo also showed that APOC2 modulated GC PM.Conclusions: We verified that knockdown of APOC2 suppressed GC cell Lipid metabolism, proliferation, migration, invasion, and EMT, accompanied by inactivation of PI3K/AKT/mTOR signaling pathway. APOC2 overexpression had the opposite effects GC cell phenotypes and mechanisms. Collectively, our results identified APOC2 in PM as a potential therapeutic target.

scholarly journals Gene Expression Profile of Dendritic Cell-Tumor Cell Hybrids Determined by Microarrays and Its Implications for Cancer Immunotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jens Dannull ◽  
Chunrui Tan ◽  
Christine Farrell ◽  
Cynthia Wang ◽  
Scott Pruitt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cell ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Cytokine Gene Expression ◽  
Mtor Signaling Pathway ◽  
T Helper 1 ◽  
Cell Hybrids ◽  
Th2 Cytokine

Background. Dendritic cell- (DC-) tumor fusion cells stimulate effectivein vivoantitumor responses. However, therapeutic approaches are dependent upon the coadministration of exogenous 3rd signals. The purpose of this study was to determine the mechanisms for inadequate 3rd signaling by electrofused DC-tumor cell hybrids.Methods. Murine melanoma cells were fused with DCs derived from C57BL/6 mice. Quantitative real-time PCR (qPCR) was used to determine relative changes in Th (T helper) 1 and Th2 cytokine gene expression. In addition, changes in gene expression of fusion cells were determined by microarray. Last, cytokine secretion by fusion cells upon inhibition of signaling pathways was analyzed by ELISA.Results. qPCR analyses revealed that fusion cells exhibited a downregulation of Th1 associated cytokines IL-12 and IL-15 and an upregulation of the Th2 cytokine IL-4. Microarray studies further showed that the expression of chemokines, costimulatory molecules, and matrix-metalloproteinases was deregulated in fusion cells. Lastly, inhibitor studies demonstrate that inhibition of the PI3K/Akt/mTOR signaling pathway could restore the secretion of bioactive IL-12p70 by fusion cells.Conclusion. Our results suggest that combining fusion cell-based vaccination with administration of inhibitors of the PI3K/Akt/mTOR signaling pathway may enhance antitumor responses in patients.

scholarly journals Mammalian Target of Rapamycin Signaling Pathway Changes with Intestinal Epithelial Cells Renewal Along Crypt-Villus Axis

2016 ◽  
Vol 39 (2) ◽  
pp. 751-759 ◽  
Author(s):  
Huansheng Yang ◽  
Xia Xiong ◽  
Xiaocheng Wang ◽  
Yulong Yin
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Antioxidant Capacity ◽  
Signaling Pathway ◽  
Intestinal Epithelial Cells ◽  
Mtor Signaling ◽  
Intestinal Epithelial ◽  
Mtor Signaling Pathway ◽  
Phosphorylation Level

Background/Aims: Understanding the mechanism that involves in regulating epithelial cells renewal is the fundamental of regulating intestinal mucosa development and functions and related diseases. The mechanistic target of rapamycin (mTOR) signaling pathway involves in controlling various major processes by integrating intracellular and extracellular cues. The present experiment was conducted to test the correlation between the mTOR signaling pathway and intestinal epithelial cells renewal along crypt-villus axis (CVA). Methods: Intestinal epithelial cells were sequentially isolated from the jejunum of piglets along CVA, and the amount or phosphorylation level of proteins involved in cell cycle, mTOR signaling pathway, gene expression, and the antioxidant capacity in the isolated cells were measured. Results: The results showed that the amount of proteins involved in cell cycle decreased from crypt to villus tip. The amount or phosphorylation level of proteins related to mTOR signaling pathway in intestinal epithelial cells mainly decreased during maturation along CVA. The amount of proteins involved in gene expression and the antioxidant capacity also decreased from crypt to the top of villi. Conclusions: These results indicate that the mTOR signaling pathway may be involved in regulating the intestinal epithelial cells renewal along CVA and it may partly through affecting the antioxidant capacity and gene expression of intestinal epithelial cells. Further histological verification is needed to confirm the results of the present experiments.

Perinatal sulfamonomethoxine exposure influences physiological and behavioral responses and the brain mTOR pathway in mouse offspring

2016 ◽  
Vol 36 (3) ◽  
pp. 256-275 ◽  
Author(s):  
Q Zhang ◽  
D Zhang ◽  
Kai-yong Liu ◽  
Ye-hao Liu ◽  
J Sheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Behavioral Responses ◽  
Female Offspring ◽  
Brain Dysfunction ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
The Brain

Sulfamonomethoxine (SMM) is widely used in the veterinary field in China. Although some clinical surveys have revealed that sulfonamide antibiotics cause adverse nervous system symptoms, the related mechanisms of maternal SMM exposure on the neurobehavioral development of offspring remain unclear. Here, we investigated the effects of perinatal SMM exposure on the physiological and behavioral responses of pubertal offspring mice and the underlying mechanisms. We randomly allocated pregnant mice into the groups treated with SMM at different doses and the saline-treated groups. Maternal mice were orally administered SMM daily from gestational day 1 to postpartum day 21. On postnatal day (PND) 22, the parameters of growth, endocrine hormones, and brain amino acid composition were assessed, as well as the brain transcript levels of key genes involved in the mammalian target of rapamycin (mTOR) signaling pathway. From PND 50 to 55, a battery of behavioral tests relevant to anxiety and memory were then administered. Analysis of the results indicated that the pups, particularly the pubertal female offspring, showed anxiety-like behavior. Moreover, the pubertal offspring showed cognitive impairments and fat accumulation. Furthermore, the relative mRNA expression of genes involved in the mTOR signaling pathway in females on PND 22 was elevated, whereas the expression of N-methyl-d-aspartate receptor 2B (NR2B) was reduced. Together, the results showed that perinatal SMM exposure perturbs neuroendocrine functions, and further alters gene expression in the mTOR pathway and NR2B gene expression early in life, which may contribute to brain dysfunction in pubertal life.

UPF1 Impacts on mTOR Signaling Pathway and Autophagy in Endometrioid Endometrial Carcinoma

2020 ◽  
Author(s):  
Minfen Zhang ◽  
Hui Chen ◽  
Ping Qin ◽  
Tonghui Cai ◽  
Lingjun Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway
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