The Expression and Significance of FAK/PI3K/AKt/mTOR Signaling Pathway Related Proteins in Human Gastric Carcinoma

2018 ◽  
Vol 08 (03) ◽  
pp. 113-120
Author(s):  
波 于
Keyword(s):  
Gastric Carcinoma ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Human Gastric Carcinoma ◽  
Related Proteins

scholarly journals Andrographolide enhanced radiosensitivity by downregulating glycolysis via the inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 colorectal cancer cells

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094616 ◽  
Author(s):  
Xiaofei Li ◽  
Ruifang Tian ◽  
Lan Liu ◽  
Lihui Wang ◽  
Dong He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Survival ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Glycolytic Activity ◽  
Related Proteins ◽  
Hct116 Cells

Objective Radiotherapy plays an important role in the treatment of colorectal cancer (CRC). However, some patients benefit minimally from radiotherapy because of radioresistance. This study investigated the effects of andrographolide on radiosensitivity in HCT116 CRC cells and examined its mechanism of action. Methods Cell survival, proliferation, apoptosis, and migration were evaluated using MTT, colony formation, flow cytometry, and Transwell cell invasion assays, respectively. Glycolysis-related indicators were measured to examine cell glycolytic activity. The expression of related proteins was detected by western blotting. Results After andrographolide treatment, the expression of phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway-related proteins, glycolytic activity, and cell survival and invasion rates were decreased in HCT116 cells. Andrographolide plus irradiation increased apoptosis and decreased survival, invasion, and colony formation compared with the effects of irradiation alone. Conclusion Andrographolide enhanced radiosensitivity by downregulating glycolysis via inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 cells.

scholarly journals Changes of Three kinds of miRNAs, MALAT1 and PI3K/AKT/mTOR signaling pathway Protein Levels in Her-2 Positive Breast Cancer in neoadjuvant chemotherapy and their relationship with prognosis- -A small sample study report

2020 ◽  
Author(s):  
Zhao Hongcan ◽  
zhang xiping
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Signaling Pathway ◽  
Chemotherapy Resistance ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Serum Samples ◽  
Before And After ◽  
Her 2 ◽  
Related Proteins ◽  
Positive Breast Cancer

Abstract Objective To investigate the roles of three kinds of miRNAs (MiR-99a, MiR-455 and MiR-143), Lnc MALAT1 and related proteins of PI3K/AKT/mTOR signaling pathway in neoadjuvant chemotherapy of patients with Her-2 positive breast cancer (BC) and analysed their related mechanisms. Method The frozen tumor tissue and serum samples before and after neoadjuvant chemotherapy of 14 cases patients with Her-2 positive BC who received neoadjuvant chemotherapy were collected. The relative expressions level of MiR-99a, MiR-455, MiR-143, MALAT1 and related proteins of PI3K/AKT/mTOR signaling pathway in tumor tissue and a part of serum samples were detected by qRT-PCR or western blot. Results MiR-99a level was negatively correlated with RFS and OS before and after chemotherapy. MiR-99a and MiR-455 levels after chemotherapy was negatively correlated with OS. The serum MALAT1 level was negatively correlated with RFS and OS in chemosensitivity group before and after chemotherapy. In chemotherapy resistance group, p-AKT level before chemotherapy was negatively correlated with T stage, p-mTOR level after chemotherapy was positively correlated with lymph node stage and negatively correlated with RFS and OS, PTEN level was negatively correlated with clinical TNM stage. Conclusion Serum MALAT1 and MiR-99a, MiR-455, MiR-143, p-AKT, p-mTOR and PTEN of tumor tissues in Her-2 positive BC patients can be used as markers to judge neoadjuvant chemotherapy sensitivity in Her-2 positive BC. Chemotherapy resistance is may be related to PI3K/AKT/mTOR signaling pathway.

scholarly journals 8-Gingerol Ameliorates Myocardial Fibrosis by Attenuating Reactive Oxygen Species, Apoptosis, and Autophagy via the PI3K/Akt/mTOR Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yucong Xue ◽  
Muqing Zhang ◽  
Miaomiao Liu ◽  
Yu Liu ◽  
Li Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Marked Decrease ◽  
Mtor Signaling ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mtor Signaling Pathway ◽  
Weight Index ◽  
Related Proteins

8-gingerol (8-Gin) is the series of phenolic substance that is extracted from ginger. Although many studies have revealed that 8-Gin has multiple pharmacological properties, the possible underlying mechanisms of 8-Gin against myocardial fibrosis (MF) remains unclear. The study examined the exact role and potential mechanisms of 8-Gin against isoproterenol (ISO)-induced MF. Male mice were intraperitoneally injected with 8-Gin (10 and 20 mg/kg/d) and concurrently subcutaneously injected with ISO (10 mg/kg/d) for 2 weeks. Electrocardiography, pathological heart morphology, myocardial enzymes, reactive oxygen species (ROS) generation, degree of apoptosis, and autophagy pathway-related proteins were measured. Our study observed 8-Gin significantly reduced J-point elevation and heart rate. Besides, 8-Gin caused a marked decrease in cardiac weight index and left ventricle weight index, serum levels of creatine kinase and lactate dehydrogenase (CK and LDH, respectively), ROS generation, and attenuated ISO-induced pathological heart damage. Moreover, treatment with 8-Gin resulted in a marked decrease in the levels of collagen types I and III and TGF-β in the heart tissue. Our results showed 8-Gin exposure significantly suppressed ISO-induced autophagosome formation. 8-Gin also could lead to down-regulation of the activities of matrix metalloproteinases-9 (MMP-9), Caspase-9, and Bax protein, up-regulation of the activity of Bcl-2 protein, and alleviation of cardiomyocyte apoptosis. Furthermore, 8-Gin produced an obvious increase in the expressions of the PI3K/Akt/mTOR signaling pathway-related proteins. Our data showed that 8-Gin exerted cardioprotective effects on ISO-induced MF, which possibly occurred in connection with inhibition of ROS generation, apoptosis, and autophagy via modulation of the PI3K/Akt/mTOR signaling pathway.

Vitexin Inhibits the Proliferation and Promotes the Apoptosis of Gastric Cancer Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (Akt)/The Mammalian Target of Rapamycin (mTOR) Signaling Pathway

2020 ◽  
Vol 10 (12) ◽  
pp. 1843-1850
Author(s):  
M. M. Jiashu Lu ◽  
M. M. Lei Yu ◽  
M. M. Ying Ma ◽  
M. M. Jie Li
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Flavonoid Compound ◽  
High Morbidity ◽  
Mtor Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Apoptosis Rate ◽  
Related Proteins

Gastric cancer (GC) is a kind of digestive tract malignancy that has very high morbidity and mortality, making it crucial to find new drug treatments. Vitexin is a kind of flavonoid compound, which has anti-tumor, anti-inflammatory, analgesic and antiviral effects, etc. However, the specific role of vitexin in GC is still unclear. In this study, the expression of the survival rate and apoptosis was detected by CCK-8 and flow cytometry after vitexin acted on cells. Plasmid transfection technique was used to overexpress PI3K. Expression of PI3K/AKT/mTOR pathway-related proteins, autophagic-related proteins (Atg14, beclin-1, P62) and apoptotic-related proteins (bcl-2, Bax, cleaved caspase3) were detected by Western blot. We found that the cell survival rate decreased with the increasing time and dosage of vitexin. When vitexin acted on cells, the expression of p-PI3K, p-AKT and p-mTOR was significantly decreased, the degree of autophagy was increased, and the apoptosis rate was obviously increased. However, the overexpression of PI3K, the level of autophagy and apoptosis rate of cells which were given vitexin significantly decreased. In conclusion, Vitexin induces autophagy by inhibiting PI3K/AKT/mTOR signaling pathway, thereby inhibiting proliferation and promoting apoptosis of GC cells.

scholarly journals Knockdown MiR-302b Alleviates LPS-Induced Injury by Targeting Smad3 in C28/I2 Chondrocytic Cells

2018 ◽  
Vol 45 (2) ◽  
pp. 733-743 ◽  
Author(s):  
Yueshu Wang ◽  
Tao Yu ◽  
Hui Jin ◽  
Changfu Zhao ◽  
Yang Wang
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Chondrocyte Apoptosis ◽  
Mtor Signaling Pathway ◽  
Smad3 Expression ◽  
Apoptosis And Inflammation ◽  
Related Proteins ◽  
Lps Treatment

Background/Aims: Osteoarthritis (OA) is one of the most common chronic degenerative diseases. Many studies have demonstrated the role of microRNAs (miRNAs) in OA; however, the role of miR-302b in OA remains elusive. The aim of this study was to identify the role of miR-302b in LPS-induced injury in chondrocytes. Methods: Human OA chondrocytes (C28/12 cell line) were transfected with miR-302b inhibitor and miR-302b mimic to investigate the effects of miR-302b expression on chondrocyte apoptosis and inflammation, and to identify the miR-302b target proteins. Results: LPS treatment of chondrocytes significantly reduced cell viability and increased apoptotic rate. LPS treatment also increased the expression of inflammatory cytokines compared to control. miR-302b was up-regulated in LPS-induced chondrocytes. miR-302b was either suppressed or overexpressed in LPS-induced chondrocytes by transient transfection. miR-302b mimic transfection accelerated the effects of LPS on cell viability, apoptosis and inflammation. Of contrast, miR-302b inhibition represented a reverse effect. Dual luciferase activity demonstrated that Smad3 is a direct target for miR-302b and its expression was negatively regulated by miR-302b. In addition, miR-302b inhibition suppressed inflammation in LPS treated chondrocytes by up-regulating Smad3 expression. Moreover, LPS induced down-regulation of Notch and mTOR signaling pathway-related protein expressions, and miR-302b inhibition increased the expressions of Notch and mTOR signaling pathway-related proteins. We further found that miR-302b negatively regulated Notch2 levels through direct targeting its 3’UTR. Conclusions: These results suggest that miR-302b suppression may function as a protector in suppressing the inflammation during the development and progression of OA by up-regulating the target Smad3 expression.

scholarly journals 17β-Estradiol Induces Mitophagy Upregulation to Protect Chondrocytes via the SIRT1-Mediated AMPK/mTOR Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Runhong Mei ◽  
Peng Lou ◽  
Guanchao You ◽  
Tianlong Jiang ◽  
Xuefeng Yu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Mtor Signaling ◽  
Sirtuin 1 ◽  
Mtor Signaling Pathway ◽  
Compound C ◽  
Transmission Electron ◽  
Sirt1 Inhibitor ◽  
17Β Estradiol ◽  
Related Proteins

Increasing evidence reveals that estrogen, especially 17β-estradiol (17β-E2), is associated with articular cartilage metabolism disorder and postmenopausal osteoarthritis (OA). SIRT1, AMPK, and mTOR are regarded as critical mitophagy regulators. Recent studies have shown that mitophagy displays a protective effect against OA, but the molecular mechanism is not well known. This study aimed to investigate the effect of 17β-E2 on Sirtuin-1 (SIRT1) expression and the induction of mitophagy upregulation by 17β-E2 via the SIRT1-mediated AMP-activated protein kinase (AMPK)/mammalian target of the rapamycin (mTOR) signaling pathway to protect chondrocytes. ATDC5 chondrocytes were treated with different concentrations of 17β-E2 (0 M, 1 × 10-9 M, 1 × 10-8 M, and 1 × 10-7 M) for 24 h or pretreatment with or without NAM (SIRT1 inhibitor), Compound C (AMPK inhibitor) and S1842 (mTOR inhibitor) for 30 min prior to treatment with 17β-E2 (1 × 10-7 M) for 24 in each groups. Expression of SIRT1 was evaluated by real-time PCR, Western blotting and confocal immunofluorescence staining. Then, the mitophagosomes in cells were observed under a transmission electron microscopy (TEM), and the AMPK/mTOR signaling pathway was detected by Western blotting. The mitophagy-related proteins, p-AMPK, p-mTOR, p-JNK, and p-p38 were also identified by Western blot analysis. The chondrocytes viability and proliferation were determined by MTT and 5-Bromo-2’-deoxyuridine (BrdU) assay. These experiments were independently repeated 3 times The study found that 17β-E2 increased the expression level of SIRT1, p-AMPK, and mitophagy-related proteins but decreased p-mTOR expression, and then induced mitophagy upregulation in chondrocytes. More mitochondrial autophagosomes were observed in 17β-E2-treated chondrocytes under a transmission electron microscope. Also, 17β-E2 improved cell viability and proliferation with the higher expression of SIRT1 and activation of the AMPK/mTOR signaling pathway. However, SIRT1 inhibitor nicotinamide (NAM) and AMPK inhibitor Compound C blocked the beneficial effect of 17β-E2. In summary, this study was novel in demonstrating that 17β-E2 induced mitophagy upregulation to protect chondrocytes via the SIRT1-mediated AMPK/mTOR signaling pathway.

scholarly journals Cordycepin augments the chemosensitivity of osteosarcoma to cisplatin by activating AMPK and suppressing the AKT signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hong-Bo Li ◽  
Jun-Kai Chen ◽  
Ze-Xin Su ◽  
Qing-Lin Jin ◽  
Li-Wen Deng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Mtor Signaling ◽  
Osteosarcoma Cell ◽  
Mtor Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Related Proteins

Abstract Background Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism. Methods CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects. Results Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway. Conclusions In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

scholarly journals Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Yongmei Li ◽  
Yuan Zhang ◽  
Guang Ji ◽  
Yiwei Shen ◽  
Nan Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sleep Deprivation ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Hepatic Function ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Deprivation Group ◽  
Mda Content ◽  
Related Proteins

Sleep deprivation adversely affects the digestive system. Multiple studies have suggested sleep deprivation and oxidative stress are closely related. Autophagy can be triggered by oxidative stress as a self-defense strategy to promote survival. In this study, we investigated the effects of sleep deprivation on liver functions, oxidative stress, and concomitant hepatocyte autophagy, as well as the associated pathways. Enzymatic and nonenzymatic biochemical markers in the serum were used to assess hepatic function and damage. To evaluate the occurrence of autophagy, expression of autophagy-related proteins was tested and autophagosomes were labeled. Additionally, methane dicarboxylic aldehyde (MDA), antioxidant enzymes, and the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were analyzed using chemical methods and a Western blot. Serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase increased in sleep-deprived rats. Total protein and albumin abundance was also abnormal. Sleep deprivation induced histopathological changes in the liver. The superoxide dismutase level decreased significantly in the liver of sleep-deprived rats. In contrast, the MDA content increased in the sleep deprivation group. Moreover, the microtubule-associated protein 1 light chain 3 beta (LC3B) II/I ratio and Beclin I content increased considerably in the sleep-deprived rats, while p62 levels decreased. Sleep deprivation apparently inhibited the AKT/mTOR signaling pathway. We conclude that sleep deprivation can induce oxidative stress and ultimately cause liver injury. Autophagy triggered by oxidative stress appears to be mediated by the AKT/mTOR pathway and plays a role in relieving oxidative stress caused by sleep deprivation.

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