α-Hederin Regulates SREBP1/FASN Pathway and Inhibits Malignant Phenotype of Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To explore the regulative effect of α-Hederin on the proliferation and invasion of NSCLC and investigate its related molecular mechanism. Methods After A549 and HCC-1833 cells were treated with a concentration gradient of α-Hederin for 24 and 48 h, the OD450nm was detected by using CCK8 assays, and the IC50 was calculated.The A549 and HCC-1833 cells were divided into the blank control and α-Hederin groups in accordance with IC50 values.Cell proliferation was detected by EdU assays, and cell cycle transformation and cell apoptosis were detected by flow cytometry.Cell mobility was detected by using Transwell and scratch assays.SREBP1 and FASN protein expression levels were detected through Western blot analysis, and cell lipid accumulation was detected via oil red O staining. Results The survival rate of lung cancer cells decreased significantly with the increase of α-Hederin concentration, and the IC50 values of A549 and HCC-1833 cells at 48 h were 15 and 25 μg/ml, respectively.Compared with the blank control group, cells proliferation and migration were significantly inhibited, cells were blocked in the G1/S phase, the apoptosis rate increased, and the protein expression and lipid accumulation of SREBP1/FASN significantly reduced after α-Hederin treatment. Conclusion α-Hederin can inhibit the proliferation and migration, G1/S phase transition and induce the apoptosis of NSCLC cells and hinder the malignant progression of NSCLC by downregulating the expression of SREBP1 and FASN and reducing the accumulation of cell lipids.

Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

TGF-β1 promotes migration and invasion of gastric cancer cells by regulating fatty acid synthase / 中国肿瘤临床

Objective: To investigate the effect of TGF-β1 on the migration and invasion of gastric cancer cells, by regulating fatty acid synthetase. Methods: From January 2016 to December 2018, 54 paraffin samples were collected from Shunde Hospital of Southern Medical University. Immunohistochemistry was used to detect the expression of transforming growth factor β1 (TGF-β1) and fatty acid synthetase (FASN) in human gastric cancer tissues, and the correlation between them was analyzed. Transient transfection of TGF-β1 and TGF-β1 siRNA was used to construct gastric cancer cell lines. Real-time PCR was used to detect FASN mRNA level, and Western blot was performed to examine FASN protein level. Transient transfection of FASN siRNA was used to construct gastric cancer cell lines. Wound healing assays and Transwell assays were performed to observe the effect of migration and invasion ability of gastric cancer cells. Results: Immunohistochemical results indicated that the expression of TGF-β1 and FASN in gastric cancer tissue was significantly positively correlated. TGF-β1 overexpression plasmid transfection significantly up-regulated the expression level of FASN mRNA and protein, whereas TGF-β1 siRNA significantly inhibited the expression of FASN. After co-transfection with FASN siRNA, TGF-β 1-induced N-cadherin protein expression was reduced and E-cadherin protein expression was enhenced. Scratch and Transwell experiments showed that the increased cell migration and invasion by TGF-β1 were significantly decreased. Conclusions: FASN plays an important role in the migration and invasion of gastric cancer cells regulated by TGF-β1.

Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis / 医学前沿

Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism, which is manifested by increased endogenous fat mobilization, hypertriglyceridemia, and increased fatty acid synthesis. Fatty acid synthase (FASN) is a key enzyme for the de novo synthesis of fatty acids, and monoacylglycerol esterase (MGLL) is an important metabolic enzyme that converts triglycerides into free fatty acids. Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways, the most common of which is the PI3K-AKT signaling pathway. They can also regulate the immune microenvironment, participate in epithelial-mesenchymal transition, and then regulate tumor invasion and metastasis. Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion. This article introduces the structures and functions of FASN and MGLL, their relationship with abnormal lipid metabolism, and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.

The effect of FASN on apoptosis in pancreatic cancer / 西安交通大学学报(医学版)

Objective To investigate the effect of fatty acid synthase (FASN)on apoptosis in pancreatic cancer cell PANC-1 and the possible molecular mechanism.Methods Annexin V/FITC and flow cytometry were performed to detect the expression of FASN in pancreatic cancer PANC-1 after C75 treatment and the change of apoptosis in pancreatic cancer cell PANC-1 treated with C75.Quantity reverse transcriptase polymerase chain reaction (RT-PCR)and Western blot were used to measure the protein and RNA expressions of Caspase-3,bcl-2 and FASN.Results Inhibited by C75,the activity of FASN in pancreatic cancer cell PANC-1 was significantly decreased.Meanwhile,PANC-1 showed an increased apoptosis level in a dose-dependent manner (P < 0.05 ). Furthermore,after C75 inhibited FASN in pancreatic cancer cells,the protein and RNA expressions of Caspase-3 significantly increased (P <0.05)whereas the level of Bcl-2 reduced (P <0.05).Conclusion FASN is involved in the process of apoptosis in PANC-1 via Bcl-2 and Caspase-3.Therefore,FASN will provide a new target for the treatment of pancreatic cancer and generate better treatment efficacy.