BLU-554, A selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro
Fibroblast growth factor receptor 4 (FGFR4) plays a key role in cancer progression, including tumour proliferation, invasion, and metastasis. Recent studies have shown that the FGFR4 selective inhibitor BLU-554 has clinical benefits on tumour regression in hepatocellular carcinoma patients. However,...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2022-03, Vol.595, p.22-27 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Zhang, Xiangjian Zhang, Xinxin Han, Ruokuo Wang, Zhaojun Yang, Qiuhui Huang, Yiming Yan, Yuxiang |
| description | Fibroblast growth factor receptor 4 (FGFR4) plays a key role in cancer progression, including tumour proliferation, invasion, and metastasis. Recent studies have shown that the FGFR4 selective inhibitor BLU-554 has clinical benefits on tumour regression in hepatocellular carcinoma patients. However, the effect of BLU-554 on gastric cancer remains unknown.
Changes in cell proliferation, apoptosis and cell cycle, migration, and invasion capabilities of MKN-45 cells treated with FGFR4 selective inhibitors were detected by CCK-8 assay, flow cytometry, transwell assay, and wound healing assay, respectively. Western blotting was used to detect the effect of BLU-554 on the expression of FGFR4, FRS2α, and p-ERK1/2.
As the concentration of the inhibitor increased, the survival rate of gastric cancer cells decreased, and the trend of BLU-554 was more obvious; a high dose of BLU-554 caused significant cell apoptosis and cell cycle arrest as well as reduced cell invasion ability. The expression levels of FGFR4, FRS2α, and p-ERK1/2 were also significantly reduced when cells were treated with medium and high doses of BLU-554.
BLU-554 inhibited the mitogen-activated protein kinase (RAS-RAF-MEK-ERK) pathway by inhibiting FGFR4, ultimately impeding the proliferation and invasion of gastric cancer cells and promoting cell apoptosis and cell cycle arrest.
•BLU-554 inhibits the proliferation and invasion of gastric cancer cells.•BLU-554 promotes cell apoptosis and cell cycle arrest of gastric cancer cells.•BLU-554 inhibits Fibroblast growth factor receptor 4.•BLU-554 inhibits the mitogen-activated protein kinase pathway. |
| doi_str_mv | 10.1016/j.bbrc.2022.01.067 |
| format | Article |
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Changes in cell proliferation, apoptosis and cell cycle, migration, and invasion capabilities of MKN-45 cells treated with FGFR4 selective inhibitors were detected by CCK-8 assay, flow cytometry, transwell assay, and wound healing assay, respectively. Western blotting was used to detect the effect of BLU-554 on the expression of FGFR4, FRS2α, and p-ERK1/2.
As the concentration of the inhibitor increased, the survival rate of gastric cancer cells decreased, and the trend of BLU-554 was more obvious; a high dose of BLU-554 caused significant cell apoptosis and cell cycle arrest as well as reduced cell invasion ability. The expression levels of FGFR4, FRS2α, and p-ERK1/2 were also significantly reduced when cells were treated with medium and high doses of BLU-554.
BLU-554 inhibited the mitogen-activated protein kinase (RAS-RAF-MEK-ERK) pathway by inhibiting FGFR4, ultimately impeding the proliferation and invasion of gastric cancer cells and promoting cell apoptosis and cell cycle arrest.
•BLU-554 inhibits the proliferation and invasion of gastric cancer cells.•BLU-554 promotes cell apoptosis and cell cycle arrest of gastric cancer cells.•BLU-554 inhibits Fibroblast growth factor receptor 4.•BLU-554 inhibits the mitogen-activated protein kinase pathway.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2022.01.067</identifier><identifier>PMID: 35093636</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adaptor Proteins, Signal Transducing - metabolism ; Anti-tumour activity ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; BLU-554 ; Cell Cycle Checkpoints - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Dose-Response Relationship, Drug ; FGFR4 selective inhibitor ; Flow Cytometry ; Gastric cancer ; Humans ; MAP Kinase Signaling System - drug effects ; Membrane Proteins - metabolism ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Pyrans - pharmacology ; Quinazolines - pharmacology ; RAS-RAF-MEK-ERK pathway ; Receptor, Fibroblast Growth Factor, Type 4 - antagonists & inhibitors ; Receptor, Fibroblast Growth Factor, Type 4 - metabolism ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology</subject><ispartof>Biochemical and biophysical research communications, 2022-03, Vol.595, p.22-27</ispartof><rights>2022 Elsevier Inc.</rights><rights>Copyright © 2022 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-34e683c9b0937390cf53b733cd77e5bb6ae1dd8e55148f0f736caedd5164b14a3</citedby><cites>FETCH-LOGICAL-c356t-34e683c9b0937390cf53b733cd77e5bb6ae1dd8e55148f0f736caedd5164b14a3</cites><orcidid>0000-0003-0200-4083</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X22000870$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35093636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xiangjian</creatorcontrib><creatorcontrib>Zhang, Xinxin</creatorcontrib><creatorcontrib>Han, Ruokuo</creatorcontrib><creatorcontrib>Wang, Zhaojun</creatorcontrib><creatorcontrib>Yang, Qiuhui</creatorcontrib><creatorcontrib>Huang, Yiming</creatorcontrib><creatorcontrib>Yan, Yuxiang</creatorcontrib><title>BLU-554, A selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Fibroblast growth factor receptor 4 (FGFR4) plays a key role in cancer progression, including tumour proliferation, invasion, and metastasis. Recent studies have shown that the FGFR4 selective inhibitor BLU-554 has clinical benefits on tumour regression in hepatocellular carcinoma patients. However, the effect of BLU-554 on gastric cancer remains unknown.
Changes in cell proliferation, apoptosis and cell cycle, migration, and invasion capabilities of MKN-45 cells treated with FGFR4 selective inhibitors were detected by CCK-8 assay, flow cytometry, transwell assay, and wound healing assay, respectively. Western blotting was used to detect the effect of BLU-554 on the expression of FGFR4, FRS2α, and p-ERK1/2.
As the concentration of the inhibitor increased, the survival rate of gastric cancer cells decreased, and the trend of BLU-554 was more obvious; a high dose of BLU-554 caused significant cell apoptosis and cell cycle arrest as well as reduced cell invasion ability. The expression levels of FGFR4, FRS2α, and p-ERK1/2 were also significantly reduced when cells were treated with medium and high doses of BLU-554.
BLU-554 inhibited the mitogen-activated protein kinase (RAS-RAF-MEK-ERK) pathway by inhibiting FGFR4, ultimately impeding the proliferation and invasion of gastric cancer cells and promoting cell apoptosis and cell cycle arrest.
•BLU-554 inhibits the proliferation and invasion of gastric cancer cells.•BLU-554 promotes cell apoptosis and cell cycle arrest of gastric cancer cells.•BLU-554 inhibits Fibroblast growth factor receptor 4.•BLU-554 inhibits the mitogen-activated protein kinase pathway.</description><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Anti-tumour activity</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>BLU-554</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>FGFR4 selective inhibitor</subject><subject>Flow Cytometry</subject><subject>Gastric cancer</subject><subject>Humans</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Membrane Proteins - metabolism</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Pyrans - pharmacology</subject><subject>Quinazolines - pharmacology</subject><subject>RAS-RAF-MEK-ERK pathway</subject><subject>Receptor, Fibroblast Growth Factor, Type 4 - antagonists & inhibitors</subject><subject>Receptor, Fibroblast Growth Factor, Type 4 - metabolism</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFOGzEQhi1URELgBXqofOyhu4zttTcr9QKogUqRkBBI3CzbO5s6Snap7UXlbfosfTIcQjlyGsnz_b_GHyGfGZQMmDpbl9YGV3LgvARWgqoPyJRBAwVnUH0iUwBQBW_Yw4Qcx7gGYKxSzRGZCAmNUEJNyepieV9IWX2j5zTiBl3yT0h9_8tbn4ZAh44urha3eY9_Xt8iNX3yRRq3wxio2fE-PVOzMr6Pia5MTME76kzvMOSif3_zPgwn5LAzm4inb3NG7hc_7i6vi-XN1c_L82XhhFSpEBWquXCNzffVogHXSWFrIVxb1yitVQZZ285RSlbNO-hqoZzBtpVMVZZVRszI133vYxh-jxiT3vrocLMxPQ5j1FzxikMOi4zyPerCEGPATj8GvzXhWTPQO8F6rXeC9U6wBqaz4Bz68tY_2i2275H_RjPwfQ9g_uWTx6Cj85hltD5ku7od_Ef9Lx_DjFc</recordid><startdate>20220305</startdate><enddate>20220305</enddate><creator>Zhang, Xiangjian</creator><creator>Zhang, Xinxin</creator><creator>Han, Ruokuo</creator><creator>Wang, Zhaojun</creator><creator>Yang, Qiuhui</creator><creator>Huang, Yiming</creator><creator>Yan, Yuxiang</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0200-4083</orcidid></search><sort><creationdate>20220305</creationdate><title>BLU-554, A selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro</title><author>Zhang, Xiangjian ; Zhang, Xinxin ; Han, Ruokuo ; Wang, Zhaojun ; Yang, Qiuhui ; Huang, Yiming ; Yan, Yuxiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-34e683c9b0937390cf53b733cd77e5bb6ae1dd8e55148f0f736caedd5164b14a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Anti-tumour activity</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>BLU-554</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>FGFR4 selective inhibitor</topic><topic>Flow Cytometry</topic><topic>Gastric cancer</topic><topic>Humans</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Membrane Proteins - metabolism</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Pyrans - pharmacology</topic><topic>Quinazolines - pharmacology</topic><topic>RAS-RAF-MEK-ERK pathway</topic><topic>Receptor, Fibroblast Growth Factor, Type 4 - antagonists & inhibitors</topic><topic>Receptor, Fibroblast Growth Factor, Type 4 - metabolism</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xiangjian</creatorcontrib><creatorcontrib>Zhang, Xinxin</creatorcontrib><creatorcontrib>Han, Ruokuo</creatorcontrib><creatorcontrib>Wang, Zhaojun</creatorcontrib><creatorcontrib>Yang, Qiuhui</creatorcontrib><creatorcontrib>Huang, Yiming</creatorcontrib><creatorcontrib>Yan, Yuxiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xiangjian</au><au>Zhang, Xinxin</au><au>Han, Ruokuo</au><au>Wang, Zhaojun</au><au>Yang, Qiuhui</au><au>Huang, Yiming</au><au>Yan, Yuxiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BLU-554, A selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2022-03-05</date><risdate>2022</risdate><volume>595</volume><spage>22</spage><epage>27</epage><pages>22-27</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Fibroblast growth factor receptor 4 (FGFR4) plays a key role in cancer progression, including tumour proliferation, invasion, and metastasis. Recent studies have shown that the FGFR4 selective inhibitor BLU-554 has clinical benefits on tumour regression in hepatocellular carcinoma patients. However, the effect of BLU-554 on gastric cancer remains unknown.
Changes in cell proliferation, apoptosis and cell cycle, migration, and invasion capabilities of MKN-45 cells treated with FGFR4 selective inhibitors were detected by CCK-8 assay, flow cytometry, transwell assay, and wound healing assay, respectively. Western blotting was used to detect the effect of BLU-554 on the expression of FGFR4, FRS2α, and p-ERK1/2.
As the concentration of the inhibitor increased, the survival rate of gastric cancer cells decreased, and the trend of BLU-554 was more obvious; a high dose of BLU-554 caused significant cell apoptosis and cell cycle arrest as well as reduced cell invasion ability. The expression levels of FGFR4, FRS2α, and p-ERK1/2 were also significantly reduced when cells were treated with medium and high doses of BLU-554.
BLU-554 inhibited the mitogen-activated protein kinase (RAS-RAF-MEK-ERK) pathway by inhibiting FGFR4, ultimately impeding the proliferation and invasion of gastric cancer cells and promoting cell apoptosis and cell cycle arrest.
•BLU-554 inhibits the proliferation and invasion of gastric cancer cells.•BLU-554 promotes cell apoptosis and cell cycle arrest of gastric cancer cells.•BLU-554 inhibits Fibroblast growth factor receptor 4.•BLU-554 inhibits the mitogen-activated protein kinase pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35093636</pmid><doi>10.1016/j.bbrc.2022.01.067</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-0200-4083</orcidid></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - metabolism Anti-tumour activity Antineoplastic Agents - pharmacology Apoptosis - drug effects BLU-554 Cell Cycle Checkpoints - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Dose-Response Relationship, Drug FGFR4 selective inhibitor Flow Cytometry Gastric cancer Humans MAP Kinase Signaling System - drug effects Membrane Proteins - metabolism Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Pyrans - pharmacology Quinazolines - pharmacology RAS-RAF-MEK-ERK pathway Receptor, Fibroblast Growth Factor, Type 4 - antagonists & inhibitors Receptor, Fibroblast Growth Factor, Type 4 - metabolism Stomach Neoplasms - metabolism Stomach Neoplasms - pathology |
| title | BLU-554, A selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro |
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