scholarly journals Downregulation of BZW2 inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway

2017 ◽  
Vol 38 (4) ◽  
pp. 2116-2122 ◽  
Author(s):  
Dong-Dong Cheng ◽  
Shi-Jie Li ◽  
Bin Zhu ◽  
Ting Yuan ◽  
Qing-Cheng Yang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Osteosarcoma Cell ◽  
Mtor Signaling Pathway

scholarly journals Ginsenoside Rg3 Suppresses Proliferation and Induces Apoptosis in Human Osteosarcoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Li ◽  
Jinying Lu ◽  
Furong Bai ◽  
Yanan Xiao ◽  
Yiran Guo ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Assay Method ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Ginsenoside Rg3 ◽  
Mtor Signaling Pathway ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Osteosarcoma is the most common primary malignancy of bone in children and the elderly. Recently, more and more researches have demonstrated that Ginsenoside Rg3 (Rg3) is involved in chemotherapy resistance in many cancer, making it a promising Chinese herbal monomer for oncotherapy. In this study, we investigated the efficacy of Rg3 in human osteosarcoma cell lines (MG-63, U-2OS, and SaOS-2). Cell proliferation was measured by CCK8 assay. The migration of cells was examined using the scratch assay method. Quantification of apoptosis was assessed further by flow cytometry. In addition, the expression of apoptosis-related genes (caspase9, caspase3, Bcl2, and Bax) were investigated using RT-PCR. We further investigated the protein level expression of Bcl 2, cleaved-caspase3, and PI3K/AKT/mTOR signaling pathway factors by Western blot assay. Our results revealed that Rg3 inhibited the proliferation and migration of human osteosarcoma cells and induced apoptosis in a concentration- and time-dependent manner. Western blot results showed that Rg3 reduced the protein expression of Bcl2 and PI3K/AKT/mTORbut increased the levels of cleaved-caspase3. Therefore, we hypothesized Rg3 inhibits the proliferation of osteosarcoma cell line and induces their apoptosis by affecting apoptosis-related genes (Bcl2, caspase3) as well as the PI3K/AKT/mTOR signaling pathway. To conclude, Rg3 is a new therapeutic agent against osteosarcoma.

Novel Gemini-vitamin D3 analog inhibits tumor cell growth and modulates the Akt/mTOR signaling pathway

2006 ◽  
Vol 100 (4-5) ◽  
pp. 107-116 ◽  
Author(s):  
James O’Kelly ◽  
Milan Uskokovic ◽  
Nathan Lemp ◽  
Jay Vadgama ◽  
H. Phillip Koeffler
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Vitamin D3 ◽  
Mtor Signaling ◽  
Tumor Cell Growth ◽  
Mtor Signaling Pathway

scholarly journals Is REDD1 a metabolic double agent? Lessons from physiology and pathology

2020 ◽  
Vol 319 (5) ◽  
pp. C807-C824
Author(s):  
Florian A. Britto ◽  
Karine Dumas ◽  
Sophie Giorgetti-Peraldi ◽  
Vincent Ollendorff ◽  
François B. Favier
Keyword(s):  
Cell Growth ◽  
Signaling Pathway ◽  
Inflammatory Diseases ◽  
Mtor Signaling ◽  
Metabolic Adaptation ◽  
Mtor Signaling Pathway ◽  
Regulate Cell Growth ◽  
Early Biomarker ◽  
Double Agent ◽  
Metabolic Stresses

The Akt/mechanistic target of rapamycin (mTOR) signaling pathway governs macromolecule synthesis, cell growth, and metabolism in response to nutrients and growth factors. Regulated in development and DNA damage response (REDD)1 is a conserved and ubiquitous protein, which is transiently induced in response to multiple stimuli. Acting like an endogenous inhibitor of the Akt/mTOR signaling pathway, REDD1 protein has been shown to regulate cell growth, mitochondrial function, oxidative stress, and apoptosis. Recent studies also indicate that timely REDD1 expression limits Akt/mTOR-dependent synthesis processes to spare energy during metabolic stresses, avoiding energy collapse and detrimental consequences. In contrast to this beneficial role for metabolic adaptation, REDD1 chronic expression appears involved in the pathogenesis of several diseases. Indeed, REDD1 expression is found as an early biomarker in many pathologies including inflammatory diseases, cancer, neurodegenerative disorders, depression, diabetes, and obesity. Moreover, prolonged REDD1 expression is associated with cell apoptosis, excessive reactive oxygen species (ROS) production, and inflammation activation leading to tissue damage. In this review, we decipher several mechanisms that make REDD1 a likely metabolic double agent depending on its duration of expression in different physiological and pathological contexts. We also discuss the role played by REDD1 in the cross talk between the Akt/mTOR signaling pathway and the energetic metabolism.

Upregulation of exosomal integrin β4 causes osteosarcoma cell proliferation via the PI3K-Akt-mTOR signaling pathway

2018 ◽  
Vol 7 (5) ◽  
pp. 1209-1220
Author(s):  
Qianrong Wang ◽  
Zhenghua Shi ◽  
Hongmei Zhang ◽  
Wenchao Liu ◽  
Zhicao Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Osteosarcoma Cell ◽  
Mtor Signaling Pathway ◽  
Integrin Β4

scholarly journals Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenpeng Cao ◽  
Zhirui Zeng ◽  
Runsang Pan ◽  
Hao Wu ◽  
Xiangyan Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Western Blot ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Cell Growth And Migration ◽  
And Migration ◽  
The Stability

BackgroundHypoxia is associated with the development of pancreatic cancer (PC). However, genes associated with hypoxia response and their regulatory mechanism in PC cells were unclear. The current study aims to investigate the role of the hypoxia associated gene fucosyltransferase 11 (FUT11) in the progression of PC.MethodsIn the preliminary study, bioinformatics analysis predicted FUT11 as a key hypoxia associated gene in PC. The expression of FUT11 in PC was evaluated using quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. The effects of FUT11 on PC cells proliferation and migration under normoxia and hypoxia were evaluated using Cell Counting Kit 8, 5-ethynyl-2’-deoxyuridine (EDU) assay, colony formation assay and transwell assay. The effects of FUT11 in vivo was examined in mouse tumor models of liver metastasis and subcutaneous xenograft. Furthermore, Western blot, luciferase assay and immunoprecipitation were performed to explore the regulatory relationship among FUT11, hypoxia-inducible factor 1α (HIF1α) and pyruvate dehydrogenase kinase 1 (PDK1) in PC.ResultsFUT11 was markedly increased of PC cells with hypoxia, upregulated in the PC clinical tissues, and predicted a poor outcome of PC patients. Inhibition of FUT11 reduced PC cell growth and migratory ability of PC cells under normoxia and hypoxia conditions in vitro, and growth and tumor cell metastasis in vivo. FUT11 bound to PDK1 and regulated the expression PDK1 under normoxia and hypoxia. FUT11 interacted with PDK1 and decreased the ubiquitination of PDK1, lead to the activation of AKT/mTOR signaling pathway. FUT11 knockdown significantly increased the degradation of PDK1 under hypoxia, while treatment with MG132 can relieve the degradation of PDK1 induced by FUT11 knockdown. Overexpression of PDK1 in PC cells under hypoxia conditions reversed the suppressive impacts of FUT11 knockdown on PC cell growth and migration. In addition, HIF1α bound to the promoter of FUT11 and increased its expression, as well as co-expressed with FUT11 in PC tissues. Furthermore, overexpression of FUT11 partially rescued the suppressive effects of HIF1α knockdown on PC cell growth and migration in hypoxia condition.ConclusionOur data implicate that hypoxia-induced FUT11 contributes to proliferation and metastasis of PC by maintaining the stability of PDK1, thus mediating activation of AKT/mTOR signaling pathway, and suggest that FUT11 could be a novel and effective target for the treatment of pancreatic cancer.

scholarly journals Chronic paraplegia-induced muscle atrophy downregulates the mTOR/S6K1 signaling pathway

2008 ◽  
Vol 104 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Hans C. Dreyer ◽  
Erin L. Glynn ◽  
Heidi L. Lujan ◽  
Christopher S. Fry ◽  
Stephen E. DiCarlo ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Mtor Signaling ◽  
Negative Regulator ◽  
Mtor Signaling Pathway ◽  
Inhibitor Of Protein Synthesis

Ribosomal S6 kinase 1 (S6K1) is a downstream component of the mammalian target of rapamycin (mTOR) signaling pathway and plays a regulatory role in translation initiation, protein synthesis, and muscle hypertrophy. AMP-activated protein kinase (AMPK) is a cellular energy sensor, a negative regulator of mTOR, and an inhibitor of protein synthesis. The purpose of this study was to determine whether the hypertrophy/cell growth-associated mTOR pathway was downregulated during muscle atrophy associated with chronic paraplegia. Soleus muscle was collected from male Sprague-Dawley rats 10 wk following complete T4–T5 spinal cord transection (paraplegic) and from sham-operated (control) rats. We utilized immunoprecipitation and Western blotting techniques to measure upstream [AMPK, Akt/protein kinase B (PKB)] and downstream components of the mTOR signaling pathway [mTOR, S6K1, SKAR, 4E-binding protein 1 (4E-BP1), and eukaryotic initiation factor (eIF) 4G and 2α]. Paraplegia was associated with significant soleus muscle atrophy (174 ± 8 vs. 240 ± 13 mg; P < 0.05). There was a reduction in phosphorylation of mTOR, S6K1, and eIF4G ( P < 0.05) with no change in Akt/PKB or 4E-BP1 ( P > 0.05). Total protein abundance of mTOR, S6K1, eIF2α, and Akt/PKB was decreased, and increased for SKAR ( P < 0.05), whereas 4E-BP1 and eIF4G did not change ( P > 0.05). S6K1 activity was significantly reduced in the paraplegic group ( P < 0.05); however, AMPKα2 activity was not altered (3.5 ± 0.4 vs. 3.7 ± 0.5 pmol·mg−1·min−1, control vs. paraplegic rats). We conclude that paraplegia-induced muscle atrophy in rats is associated with a general downregulation of the mTOR signaling pathway. Therefore, in addition to upregulation of atrophy signaling during muscle wasting, downregulation of muscle cell growth/hypertrophy-associated signaling appears to be an important component of long-term muscle loss.

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