Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells
| Autor: | Shu-Yao Tsai, Mei Due Yang, En-Pei Isabel Chiang, Cheng-Chieh Lin, Jia-Ning Syu, Feng-Yao Tang, Hung-Yu Lin, Yen-Huang Cheng, Che-Yi Chao |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell signaling
Physiology medicine.medical_treatment Protein Expression Retinoic Acid Retinoic acid Cancer Treatment Organic chemistry Signal transduction Biochemistry chemistry.chemical_compound Cell Movement Immune Physiology Medicine and Health Sciences Metabolites Vitamin D Phosphorylation Isotretinoin Anthracenes Innate Immune System Multidisciplinary Kinase NF-kappa B Signaling cascades Vitamins c-Jun N-terminal kinase signaling cascade Up-Regulation Chemistry Cytokine Oncology Matrix Metalloproteinase 9 Physical Sciences Medicine Cytokines Tumor necrosis factor alpha Research Article Cell biology Signal Inhibition General Science & Technology Cell Survival MAP Kinase Signaling System Science Immunology Adenocarcinoma Research and Analysis Methods Transfection Pancreatic Cancer Downregulation and upregulation Calcitriol Pancreatic cancer Cell Line Tumor Gastrointestinal Tumors Organic compounds medicine Gene Expression and Vector Techniques Humans Neoplasm Invasiveness Molecular Biology Techniques Molecular Biology Tissue Inhibitor of Metalloproteinase-3 Molecular Biology Assays and Analysis Techniques Tumor Necrosis Factor-alpha Chemical Compounds JNK Mitogen-Activated Protein Kinases Biology and Life Sciences Cancers and Neoplasms Molecular Development medicine.disease Pancreatic Neoplasms MicroRNAs Metabolism chemistry Immune System Cancer cell Cancer research Acids Developmental Biology |
| Zdroj: | PLoS ONE PloS one, vol 16, iss 3 PLoS ONE, Vol 16, Iss 3, p e0247550 (2021) |
| ISSN: | 1932-6203 |
| Popis: | Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC. |
| Databáze: | OpenAIRE |
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