MIF inhibitor, ISO-1, attenuates human pancreatic cancer cell proliferation, migration and invasion in vitro, and suppresses xenograft tumour growth in vivo

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...

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Veröffentlicht in:Scientific reports 2020-04, Vol.10 (1), p.6741-6741, Article 6741
Hauptverfasser: Cheng, Bo, Wang, Qiaofang, Song, Yaodong, Liu, Yanna, Liu, Yanyan, Yang, Shujun, Li, Dejian, Zhang, Yan, Zhu, Changju
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container_title Scientific reports
container_volume 10
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Wang, Qiaofang
Song, Yaodong
Liu, Yanna
Liu, Yanyan
Yang, Shujun
Li, Dejian
Zhang, Yan
Zhu, Changju
description 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.
doi_str_mv 10.1038/s41598-020-63778-y
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-63778-y</identifier><identifier>PMID: 32317702</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154 ; 631/67 ; Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Animals ; Antineoplastic Agents - pharmacology ; Biological Assay ; Biological effects ; Cell adhesion &amp; migration ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cholecystokinin ; Diffusion Chambers, Culture ; Enzyme Inhibitors - pharmacology ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Humanities and Social Sciences ; Humans ; Intramolecular Oxidoreductases - genetics ; Intramolecular Oxidoreductases - metabolism ; Isoxazoles - pharmacology ; Kinases ; Macrophage Migration-Inhibitory Factors - genetics ; Macrophage Migration-Inhibitory Factors - metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; mRNA ; multidisciplinary ; Neoplasm Invasiveness ; NF-κB protein ; Pancreatic cancer ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Recolonization ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Science ; Science (multidisciplinary) ; Signal Transduction ; Therapeutic applications ; Transcription Factor RelA - genetics ; Transcription Factor RelA - metabolism ; Tumor Burden - drug effects ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>Scientific reports, 2020-04, Vol.10 (1), p.6741-6741, Article 6741</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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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 . 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Wang, Qiaofang ; Song, Yaodong ; Liu, Yanna ; Liu, Yanyan ; Yang, Shujun ; Li, Dejian ; Zhang, Yan ; Zhu, Changju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-dd2d35fc1f65f02614ebd11485eb61c53e9ee3ae5f8b3b61f72943ed6b1e3ea73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/154</topic><topic>631/67</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological Assay</topic><topic>Biological effects</topic><topic>Cell adhesion &amp; migration</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cholecystokinin</topic><topic>Diffusion Chambers, Culture</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Intramolecular Oxidoreductases - genetics</topic><topic>Intramolecular Oxidoreductases - metabolism</topic><topic>Isoxazoles - pharmacology</topic><topic>Kinases</topic><topic>Macrophage Migration-Inhibitory Factors - genetics</topic><topic>Macrophage Migration-Inhibitory Factors - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>mRNA</topic><topic>multidisciplinary</topic><topic>Neoplasm Invasiveness</topic><topic>NF-κB protein</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Recolonization</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction</topic><topic>Therapeutic applications</topic><topic>Transcription Factor RelA - genetics</topic><topic>Transcription Factor RelA - metabolism</topic><topic>Tumor Burden - drug effects</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-α</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Bo</creatorcontrib><creatorcontrib>Wang, Qiaofang</creatorcontrib><creatorcontrib>Song, Yaodong</creatorcontrib><creatorcontrib>Liu, Yanna</creatorcontrib><creatorcontrib>Liu, Yanyan</creatorcontrib><creatorcontrib>Yang, Shujun</creatorcontrib><creatorcontrib>Li, Dejian</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Zhu, Changju</creatorcontrib><collection>SpringerOpen (Open Access)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32317702</pmid><doi>10.1038/s41598-020-63778-y</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects 631/154
631/67
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Animals
Antineoplastic Agents - pharmacology
Biological Assay
Biological effects
Cell adhesion & migration
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement - drug effects
Cell proliferation
Cell Proliferation - drug effects
Cholecystokinin
Diffusion Chambers, Culture
Enzyme Inhibitors - pharmacology
Female
Gene expression
Gene Expression Regulation, Neoplastic
Humanities and Social Sciences
Humans
Intramolecular Oxidoreductases - genetics
Intramolecular Oxidoreductases - metabolism
Isoxazoles - pharmacology
Kinases
Macrophage Migration-Inhibitory Factors - genetics
Macrophage Migration-Inhibitory Factors - metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
mRNA
multidisciplinary
Neoplasm Invasiveness
NF-κB protein
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Recolonization
RNA, Messenger - genetics
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
Signal Transduction
Therapeutic applications
Transcription Factor RelA - genetics
Transcription Factor RelA - metabolism
Tumor Burden - drug effects
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-α
Tumors
Xenograft Model Antitumor Assays
Xenografts
title MIF inhibitor, ISO-1, attenuates human pancreatic cancer cell proliferation, migration and invasion in vitro, and suppresses xenograft tumour growth in vivo
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