Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway
Aberrant Wnt signaling pathway is associated with a wide array of tumor types and plays an important role in the drug resistance of cancer stem cells (CSCs). To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cell...
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| Veröffentlicht in: | International journal of oncology 2016-04, Vol.48 (4), p.1333-1340 |
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| creator | WU, XUEFANG LUO, FENG LI, JINBANG ZHONG, XUEYUN LIU, KUNPING |
| description | Aberrant Wnt signaling pathway is associated with a wide array of tumor types and plays an important role in the drug resistance of cancer stem cells (CSCs). To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cells SW480 and SW620 were treated with 5-fluorouracil (5-FU)/cisplatin (DDP) alone or combined with XAV939. Cell cycle distribution, apoptosis level and the percentage of CD133+ cells were detected by flow cytometry. The protein expression of Axin, β-catenin, EpCAM, TERT and DCAMKL-1 was detected by western blotting. XAV939 upregulated Axin, decreased the total and nuclei of β-catenin in SW480 and SW620 cells. Furthermore, XAV939 significantly downregulated the CSC markers EpCAM, TERT and DCAMKL-1 in SW480 cells, as well as EpCAM in SW620 cells. No significant difference was found in the apoptosis of SW480 and SW620 cells with XAV939 treatment, but XAV939 significantly increased apoptosis induced by 5-FU/DDP in SW480 cells, whereas, the effects were slight in SW620 cells. Collectively, we show for the first time that the WNT signaling pathway inhibitor XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of β-catenin, Axin and CSC markers in colon cancer cells. Axin, an important component of Wnt/β-catenin signaling pathway could be a potential molecular target for reversing multidrug resistance in colon cancer. |
| doi_str_mv | 10.3892/ijo.2016.3360 |
| format | Article |
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To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cells SW480 and SW620 were treated with 5-fluorouracil (5-FU)/cisplatin (DDP) alone or combined with XAV939. Cell cycle distribution, apoptosis level and the percentage of CD133+ cells were detected by flow cytometry. The protein expression of Axin, β-catenin, EpCAM, TERT and DCAMKL-1 was detected by western blotting. XAV939 upregulated Axin, decreased the total and nuclei of β-catenin in SW480 and SW620 cells. Furthermore, XAV939 significantly downregulated the CSC markers EpCAM, TERT and DCAMKL-1 in SW480 cells, as well as EpCAM in SW620 cells. No significant difference was found in the apoptosis of SW480 and SW620 cells with XAV939 treatment, but XAV939 significantly increased apoptosis induced by 5-FU/DDP in SW480 cells, whereas, the effects were slight in SW620 cells. Collectively, we show for the first time that the WNT signaling pathway inhibitor XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of β-catenin, Axin and CSC markers in colon cancer cells. Axin, an important component of Wnt/β-catenin signaling pathway could be a potential molecular target for reversing multidrug resistance in colon cancer.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2016.3360</identifier><identifier>PMID: 26820603</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Axin Protein - biosynthesis ; Axin Protein - genetics ; beta Catenin - biosynthesis ; beta Catenin - genetics ; cancer stem cells ; Cancer therapies ; Cell cycle ; Cell division ; Cell growth ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cellular signal transduction ; Chemotherapy ; Cisplatin - administration & dosage ; Colon cancer ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; Colorectal cancer ; Drug resistance ; Drug Resistance, Neoplasm - drug effects ; Enzyme inhibitors ; Experiments ; Flow cytometry ; Fluorouracil - administration & dosage ; Gene Expression Regulation, Neoplastic - drug effects ; Heterocyclic Compounds, 3-Ring - administration & dosage ; Humans ; Mutation ; Neoplastic Stem Cells - drug effects ; Observations ; Pharmaceuticals ; Protein expression ; Proteins ; Software ; Statistical analysis ; Stem cells ; Studies ; Tankyrases - antagonists & inhibitors ; Tankyrases - genetics ; Testing ; Tumors ; Variance analysis ; WNT signaling pathway ; Wnt Signaling Pathway - drug effects ; XAV939</subject><ispartof>International journal of oncology, 2016-04, Vol.48 (4), p.1333-1340</ispartof><rights>Copyright: © Wu et al.</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><rights>Copyright: © Wu et al. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545t-4b73cfd539ebeb69000ca3ba4a53fdbfeff057caeb7a56336cb8138fa155298c3</citedby><cites>FETCH-LOGICAL-c545t-4b73cfd539ebeb69000ca3ba4a53fdbfeff057caeb7a56336cb8138fa155298c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,5556,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26820603$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WU, XUEFANG</creatorcontrib><creatorcontrib>LUO, FENG</creatorcontrib><creatorcontrib>LI, JINBANG</creatorcontrib><creatorcontrib>ZHONG, XUEYUN</creatorcontrib><creatorcontrib>LIU, KUNPING</creatorcontrib><title>Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Aberrant Wnt signaling pathway is associated with a wide array of tumor types and plays an important role in the drug resistance of cancer stem cells (CSCs). To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cells SW480 and SW620 were treated with 5-fluorouracil (5-FU)/cisplatin (DDP) alone or combined with XAV939. Cell cycle distribution, apoptosis level and the percentage of CD133+ cells were detected by flow cytometry. The protein expression of Axin, β-catenin, EpCAM, TERT and DCAMKL-1 was detected by western blotting. XAV939 upregulated Axin, decreased the total and nuclei of β-catenin in SW480 and SW620 cells. Furthermore, XAV939 significantly downregulated the CSC markers EpCAM, TERT and DCAMKL-1 in SW480 cells, as well as EpCAM in SW620 cells. No significant difference was found in the apoptosis of SW480 and SW620 cells with XAV939 treatment, but XAV939 significantly increased apoptosis induced by 5-FU/DDP in SW480 cells, whereas, the effects were slight in SW620 cells. Collectively, we show for the first time that the WNT signaling pathway inhibitor XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of β-catenin, Axin and CSC markers in colon cancer cells. Axin, an important component of Wnt/β-catenin signaling pathway could be a potential molecular target for reversing multidrug resistance in colon cancer.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Axin Protein - biosynthesis</subject><subject>Axin Protein - genetics</subject><subject>beta Catenin - biosynthesis</subject><subject>beta Catenin - genetics</subject><subject>cancer stem cells</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell division</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cellular signal transduction</subject><subject>Chemotherapy</subject><subject>Cisplatin - administration & dosage</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Enzyme inhibitors</subject><subject>Experiments</subject><subject>Flow cytometry</subject><subject>Fluorouracil - administration & dosage</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Heterocyclic Compounds, 3-Ring - administration & dosage</subject><subject>Humans</subject><subject>Mutation</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Observations</subject><subject>Pharmaceuticals</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Software</subject><subject>Statistical analysis</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Tankyrases - antagonists & inhibitors</subject><subject>Tankyrases - genetics</subject><subject>Testing</subject><subject>Tumors</subject><subject>Variance analysis</subject><subject>WNT signaling pathway</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>XAV939</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkt2LEzEUxQdR3HX10VcJCOvT1HzP5EUoi6vCgi_rx1vIZJJO6jSpybTSp_3XvaVrdwsmkISc3z1wL6eqXhM8Y62i78MyzSgmcsaYxE-qc9IoUlNO2VN4Y6JqyZk6q16UssSYCoHJ8-qMypZiidl5dXdr4q9dNsUhgkIcQhemkDL6Of-umIIfmx2IBdnBrVJxsYC-DdMOJGTTmOA00bqMrBtHNIYI7DaYB6-IkkfT4NCPOKESFtEAtEBrMw1_zO5l9cybsbhX9_dF9e364-3V5_rm66cvV_Ob2gouppp3DbO-F0y5znVSYYytYZ3hRjDfd955j0VjjesaIySMwnYtYa03RAiqWssuqg8H3_WmW7neujhlM-p1DiuTdzqZoE-VGAa9SFvNm6YRSoLB23uDnH5vXJn0Mm0yNFM0UYwyqlgrHqiFGZ0O0Scws6tQrJ5zrqTkhDRAzf5Dwe7dKtgUnQ_wf1Jw-ahgcGachpLGzX685RSsD6DNqZTs_LFDgvU-Lxryovd50fu8AP_m8ViO9L-AAPDuAJS1iX3oUzky4FTztsa8JgzWXymiyb8</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>WU, XUEFANG</creator><creator>LUO, FENG</creator><creator>LI, JINBANG</creator><creator>ZHONG, XUEYUN</creator><creator>LIU, KUNPING</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20160401</creationdate><title>Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway</title><author>WU, XUEFANG ; LUO, FENG ; LI, JINBANG ; ZHONG, XUEYUN ; LIU, KUNPING</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c545t-4b73cfd539ebeb69000ca3ba4a53fdbfeff057caeb7a56336cb8138fa155298c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Axin Protein - biosynthesis</topic><topic>Axin Protein - genetics</topic><topic>beta Catenin - biosynthesis</topic><topic>beta Catenin - genetics</topic><topic>cancer stem cells</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell division</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cellular signal transduction</topic><topic>Chemotherapy</topic><topic>Cisplatin - administration & dosage</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Enzyme inhibitors</topic><topic>Experiments</topic><topic>Flow cytometry</topic><topic>Fluorouracil - administration & dosage</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Heterocyclic Compounds, 3-Ring - administration & dosage</topic><topic>Humans</topic><topic>Mutation</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Observations</topic><topic>Pharmaceuticals</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Software</topic><topic>Statistical analysis</topic><topic>Stem cells</topic><topic>Studies</topic><topic>Tankyrases - antagonists & inhibitors</topic><topic>Tankyrases - genetics</topic><topic>Testing</topic><topic>Tumors</topic><topic>Variance analysis</topic><topic>WNT signaling pathway</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>XAV939</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WU, XUEFANG</creatorcontrib><creatorcontrib>LUO, FENG</creatorcontrib><creatorcontrib>LI, JINBANG</creatorcontrib><creatorcontrib>ZHONG, XUEYUN</creatorcontrib><creatorcontrib>LIU, KUNPING</creatorcontrib><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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WU, XUEFANG</au><au>LUO, FENG</au><au>LI, JINBANG</au><au>ZHONG, XUEYUN</au><au>LIU, KUNPING</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>48</volume><issue>4</issue><spage>1333</spage><epage>1340</epage><pages>1333-1340</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><abstract>Aberrant Wnt signaling pathway is associated with a wide array of tumor types and plays an important role in the drug resistance of cancer stem cells (CSCs). To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cells SW480 and SW620 were treated with 5-fluorouracil (5-FU)/cisplatin (DDP) alone or combined with XAV939. Cell cycle distribution, apoptosis level and the percentage of CD133+ cells were detected by flow cytometry. The protein expression of Axin, β-catenin, EpCAM, TERT and DCAMKL-1 was detected by western blotting. XAV939 upregulated Axin, decreased the total and nuclei of β-catenin in SW480 and SW620 cells. Furthermore, XAV939 significantly downregulated the CSC markers EpCAM, TERT and DCAMKL-1 in SW480 cells, as well as EpCAM in SW620 cells. No significant difference was found in the apoptosis of SW480 and SW620 cells with XAV939 treatment, but XAV939 significantly increased apoptosis induced by 5-FU/DDP in SW480 cells, whereas, the effects were slight in SW620 cells. Collectively, we show for the first time that the WNT signaling pathway inhibitor XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of β-catenin, Axin and CSC markers in colon cancer cells. Axin, an important component of Wnt/β-catenin signaling pathway could be a potential molecular target for reversing multidrug resistance in colon cancer.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26820603</pmid><doi>10.3892/ijo.2016.3360</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of oncology, 2016-04, Vol.48 (4), p.1333-1340 |
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| subjects | Apoptosis Apoptosis - drug effects Axin Protein - biosynthesis Axin Protein - genetics beta Catenin - biosynthesis beta Catenin - genetics cancer stem cells Cancer therapies Cell cycle Cell division Cell growth Cell Line, Tumor Cell Proliferation - drug effects Cellular signal transduction Chemotherapy Cisplatin - administration & dosage Colon cancer Colonic Neoplasms - drug therapy Colonic Neoplasms - genetics Colonic Neoplasms - pathology Colorectal cancer Drug resistance Drug Resistance, Neoplasm - drug effects Enzyme inhibitors Experiments Flow cytometry Fluorouracil - administration & dosage Gene Expression Regulation, Neoplastic - drug effects Heterocyclic Compounds, 3-Ring - administration & dosage Humans Mutation Neoplastic Stem Cells - drug effects Observations Pharmaceuticals Protein expression Proteins Software Statistical analysis Stem cells Studies Tankyrases - antagonists & inhibitors Tankyrases - genetics Testing Tumors Variance analysis WNT signaling pathway Wnt Signaling Pathway - drug effects XAV939 |
| title | Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway |
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