ABSTRACT
PGAM5 has been associated with the development of tumours, however, its function in gastric cancer (GC) remains unexplored. Here, we investigated the role and mechanism of PGAM5 in regulating GC. The results revealed that PGAM5 was upregulated in GC tissues and cell lines, which was correlated with tumour size and TNM stage. Moreover, PGAM5 knockdown inhibited proliferation, migration, and invasion progression, whereas PGAM5 overexpression promoted the function of GC cells in vitro. PGAM5 also promoted the activation of the PI3K/AKT signalling pathway. Furthermore, MK-2206, an AKT inhibitor, reversed the proliferation and activation of the PI3K/AKT signalling pathway induced by PGAM5 knockdown in GC cells. In conclusion, PGAM5 promotes the proliferation of GC by positively regulating the activation of the PI3K/AKT signalling pathway in GC cells.
Subject(s)
Proto-Oncogene Proteins c-akt , Stomach Neoplasms , Humans , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , Cell Transformation, Neoplastic , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Phosphoprotein Phosphatases/metabolism , Mitochondrial Proteins/metabolismABSTRACT
PURPOSE: To detect the expression of AGO1 in cholangiocarcinoma and explore its role and significance in the progression of cholangiocarcinoma. PATIENTS AND METHODS: Using immunohistochemistry, Western blotting and qPCR, we examined the expression of AGO1 in cholangiocarcinoma tissues. Through the analysis of clinical case data, the relationship between AGO1 and clinical prognosis was explored. The effect of AGO1 on cholangiocarcinoma was verified by cell functional experiments. Finally, we examined the effects of AGO1 on EMT-related proteins and signaling pathways. RESULTS: AGO1 is significantly upregulated in cholangiocarcinoma and is associated with the prognosis of cholangiocarcinoma. AGO1 can significantly increase the proliferation, migration and invasion of cholangiocarcinoma cell lines. AGO1 affects the prognosis of cholangiocarcinoma by affecting epithelial-mesenchymal transition (EMT)-related TGF-ß-PI3K-AKT signaling pathways. CONCLUSION: AGO1 is an independent predictor of cholangiocarcinoma prognosis and a potential target for the treatment of cholangiocarcinoma.
ABSTRACT
BACKGROUND/AIM: Double-negative T (DNT) cells are phenotypically CD3+CD4-CD8-T cells. This study aimed to investigate the anti-cancer activity of DNT cells against pancreatic cancer cells. MATERIALS AND METHODS: DNT cells were isolated from human peripheral blood. The effect of DNT cells on proliferation and invasion of the human pancreatic cell line Panc-1 was assessed. Expression of Nrf2 and Fas in Panc-1 cells co-cultured with DNT cells was analyzed with RT-PCR. The supernatants of Panc-1 and DNT co-cultures were analyzed with ELISA for IFN-r and FasL levels. RESULTS: The isolated DNT cell phenotype was CD4-CD8-CD56- CD3+TCR (T cell receptor) α/ß+ T cells with more than 90% purity. Panc-1 cell proliferation was significantly inhibited by co-culture with DNT cells. Panc-1 cells co-cultured with DNT cells showed significantly reduced cell invasion. Panc-1 cells co-cultured with DNT cells showed increased Nrf2 and Fas mRNA expression. Increased INF-r and FasL levels were detected in the supernatants of co-cultures of DNT and pancreatic cells. CONCLUSION: DNT cells inhibited proliferation and invasion of human pancreatic cancer cells. The INF-r, Fas/FasL pathway and Nrf2 may be involved in the anti-cancer effect of DNT cells against human pancreatic cancer.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coculture Techniques/methods , Lymphocyte Activation/immunology , Pancreatic Neoplasms/prevention & control , Apoptosis , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Proliferation , Fas Ligand Protein/metabolism , Humans , NF-E2-Related Factor 2/metabolism , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Receptors, Interferon/metabolism , Tumor Cells, Cultured , fas Receptor/metabolismABSTRACT
OBJECTIVES: This study aimed to explore double-negative T (DNT) cell cytotoxicity to pancreatic cancer and the effect of the Fas (CD95, APO-1)/FasL (CD178) signaling pathway on this process. METHODS: DNT cells from the peripheral blood of healthy volunteers were expanded in vitro. The inhibitory effect of DNT cells on pancreatic cancer cells was investigated using a CCK-8 assay and nude mouse tumor model. A mechanistic study was performed using pathway blocking assays. RESULTS: DNT cells were amplified in vitro with >90% purity, and the growth of pancreatic cancer in vitro was significantly inhibited by DNT cells. After coculture with DNT cells, Fas, caspase-8 and cleaved caspase-8 showed increased expression in pancreatic cancer cells. When blocking agent decoy receptor 3 (DcR3) was added, the antitumor effect of DNT cells and the expression of Fas, caspase-8 and cleaved caspase-8 were reduced in pancreatic cancer cells. In the nude mouse tumor model, the tumor volume and weight were lower in the DNT cell group and gemcitabine group than in the blank control group. Additionally, the expression of Fas, caspase-8 and cleaved caspase-8 was higher in the DNT cell group than in the blank control group. Moreover, DNT cells promoted apoptosis in cancer cells and animal model tissues. CONCLUSION: DNT cells inhibited the growth of pancreatic cancer, and the Fas/FasL signaling pathway was involved in this process.