Abstract
This study sought to investigate the biological effects of specific MIF inhibitor, ISO-1, on the proliferation, migration and invasion of PANC-1 human pancreatic cells in vitro, and on tumour growth in a xenograft tumour model in vivo. The effect of ISO-1 on PANC-1 cell proliferation was examined using CCK-8 cell proliferation assay. The effect of ISO-1 on collective cell migration and recolonization of PANC-1 cells was evaluated using the cell-wound closure migration assay. The effect of ISO-1 on the migration and invasion of individual PANC-1 cells in a 3-dimensional environment in response to a chemo-attractant was investigated through the use of Transwell migration/invasion assays. Quantitative real time PCR and western blot analyses were employed to investigate the effects of ISO-1 on MIF, NF-κB p65 and TNF-α mRNA and protein expression respectively. Finally, a xenograft tumor model in BALB/c nude mice were used to assess the in vivo effects of ISO-1 on PANC-1-induced tumor growth. We found high expression of MIF in pancreatic cancer tissues. We demonstrated that ISO-1 exerts anti-cancer effects on PANC-1 cell proliferation, migration and invasion in vitro, and inhibited PANC-1 cell-induced tumour growth in xenograft mice in vivo. Our data suggests that ISO-1 and its derivative may have potential therapeutic applications in pancreatic cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Animals
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Antineoplastic Agents / pharmacology*
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Biological Assay
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Diffusion Chambers, Culture
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Enzyme Inhibitors / pharmacology*
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Female
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Gene Expression Regulation, Neoplastic*
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Humans
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Intramolecular Oxidoreductases / genetics*
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Intramolecular Oxidoreductases / metabolism
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Isoxazoles / pharmacology*
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Macrophage Migration-Inhibitory Factors / genetics*
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Macrophage Migration-Inhibitory Factors / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Invasiveness
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Pancreatic Neoplasms / drug therapy*
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Signal Transduction
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism
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Tumor Burden / drug effects
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Xenograft Model Antitumor Assays
Substances
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3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester
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Antineoplastic Agents
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Enzyme Inhibitors
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Isoxazoles
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Macrophage Migration-Inhibitory Factors
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RNA, Messenger
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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Intramolecular Oxidoreductases
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MIF protein, human