Interference of lysine-specific demethylase 1 inhibits cellular invasion and proliferation in vivo in gastric cancer MKN-28 cells |
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| Affiliation: | 1. Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, China;2. Department of Oncology, The First Affiliated Hospital of China Medical University, China;1. Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;2. Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada;3. Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;4. Division of Radiation Oncology, Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada;5. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;6. Division of Medical Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada;7. Division of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;1. Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14640, USA;2. Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;3. MTA-DE Lendület Laboratory of Cellular Metabolism Research Group, Debrecen, Hungary;4. Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;2. Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, CA 92093, United States;3. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;4. Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt;5. Department of Natural Products, China Pharmaceutical University, Nanjing 210009, China;6. Graduate University of Chinese Academy of Sciences, Beijing 100049, China;7. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;8. Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia;1. School of Life Sciences, Jinlin University, Changchun 130012, China;2. College of Pharmacy, The Ohio State University, Columbus 43210, USA |
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| Abstract: | BackgroundLysine-specific demethylase 1(LSD1), the first identified histone demethylase, plays an important role in the epigenetic regulation of gene activation and repression. Up-regulated LSD1expression has been reported in several malignant tumors.Our aim, therefore, was to better understand the mechanisms underlying the upregulation of LSD1 in gastric cancer.MethodsWe used lentiviral shRNA to knockdown LSD1 in the gastric cancer MKN-28 cell line. Cell proliferation was measured by MTT assay while cell apoptosis was assessed by Annexin V-FITC/PI double staining flow cytometry. The invasive potential of gastric cancer cells was determined by matrigel invasion assay. Protein expression was detected by Western blot. In vivo, the effect of knocking down LSD1 on tumor growth and protein expression in gastric cancer cells in nude mice was investigated.ResultsLSD1 knockdown in MKN-28 cell lines resulted in increasing the activity of cisplatin in vitro and the inhibition of cancer cell proliferation and invasion, and induced cell apoptosis. The expression of TGF-β1, VEGF, Bcl-2, β-catenin, p-ERK and p-Smad 2/3 proteins was inhibited in LSD1 knockdown cells. Moreover, in an in vivo model of gastric cancer, LSD1 knockdown suppressed tumor growth and protein expression.ConclusionLSD1 knockdown affected the fuction of gastric cancer MKN-28 cell line. LSD1 may be a latent target in the diagnosis and therapy of gastric cancer. |
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| Keywords: | Lentivirus shRNA LSD1 Cisplatin Gastric cancer |
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