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.

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.

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.

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