Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma
Background Two chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors...
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| Veröffentlicht in: | Egyptian Liver Journal 2023-12, Vol.13 (1), p.29-9, Article 29 |
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| creator | Sekar, Vasanthakumar Veerabathiran, Ramakrishnan Pandian, Arjun Sivamani, Ganesan |
| description | Background
Two chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors such as hypoxia, cancer stem cells, and drug efflux mechanism cancer stem cells (CSC) which are significant factors involved in chemoresistance. It has been exposed that targeting liver cancer stem cells and chemotherapeutic drugs have a better selected, overall survival rate for hepatocellular carcinoma patients.
Aim
This study aims to investigate the effectiveness of targeting stem cells for liver cancer using a therapy that targets EpCAM in combination with chemotherapy and how this approach can enhance the treatment outcomes in hepatocellular carcinoma, the most prevalent kind of liver cancer.
Results
The outcome was studied by flow cytometry, Western blot, RT-PCR, and cytotoxicity assays. EpCAM gene silenced and XAV939-treated cells showed decreased expression of CD133, a liver cancer stem cell (LCSC) marker in flow cytometry analysis, and reduced expression of ABCG2 gene, which is a reliable marker for chemoresistance in RT-PCR and western blot analysis; it was also unable to form colonies in colony forming assay. Similarly, in the spheroid formation assay, EpCAM gene silenced cells and XAV939-treated cells in combinations with cisplatin treatment were powerless to appear spheroid, whereas cisplatin alone-treated cells showed spheroids. In the cytotoxicity assay, cisplatin alone and combined with EpCAM silenced and XAV939-treated cells showed more lactate dehydrogenase (LDH) release than EpCAM silenced arm XAV939 treated components.
Conclusion
These findings confirm our hypothesis that conventional chemotherapy kills cancer cells but not cancer stem cells. We believe EpCAM-targeted therapy enhances chemosensitivity and decreases relapsed chances. This approach might be the best option for a better prognosis for hepatocellular carcinoma patients. |
| doi_str_mv | 10.1186/s43066-023-00263-x |
| format | Article |
| fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_proquest_journals_2827009515</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A753262388</galeid><doaj_id>oai_doaj_org_article_107b48838b80435c982424f619b3375a</doaj_id><sourcerecordid>A753262388</sourcerecordid><originalsourceid>FETCH-LOGICAL-c496t-d08d4ece5b21ccb7d3fb8b2fdcdc3a251aa1734ae2025b0936c0e49eebe5abc33</originalsourceid><addsrcrecordid>eNp9Uk1v1DAQjRBIVNv-AU6WOKf4I3Gc42pVoFIRl3K2_DFJvErsYHuh_Qv8ary7QIuEsA8zHr_3ZkZ6VfWG4GtCBH-XGoY5rzFlNcaUs_rhRXVBcY9rTil_-Sx_XV2ltMflCNJh1l1UP-5VHCE7P6LZfYOIjPKmhJRhQQbmGeUphsM4oZt1t_1UXhDV-ojyiQYWfXd5QmaCJfz-Am9DTFDidNSyaI1hjJCSCx45jyZYVQ5H7cOsjg2jcT4s6rJ6Nag5wdWvuKm-vL-5332s7z5_uN1t72rT9DzXFgvbgIFWU2KM7iwbtNB0sMYapmhLlCIdaxRQTFuNe8YNhqYH0NAqbRjbVLdnXRvUXq7RLSo-yqCcPBVCHKWK2ZkZJMGdboRgQgvcsNb0gja0GTjpNWNdq4rW27NW2fHrAVKW-3CIvowvqaAdxn1L2ifUqIqo80PIUZnFJSO3Xcsop6w02VTX_0CVa2FxJngYXKn_RaBngokhpQjDn2UIlkdnyLMzZHGGPDlDPhQSO5NSAfsR4tPE_2H9BI2bvWE</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2827009515</pqid></control><display><type>article</type><title>Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma</title><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><creator>Sekar, Vasanthakumar ; Veerabathiran, Ramakrishnan ; Pandian, Arjun ; Sivamani, Ganesan</creator><creatorcontrib>Sekar, Vasanthakumar ; Veerabathiran, Ramakrishnan ; Pandian, Arjun ; Sivamani, Ganesan</creatorcontrib><description>Background
Two chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors such as hypoxia, cancer stem cells, and drug efflux mechanism cancer stem cells (CSC) which are significant factors involved in chemoresistance. It has been exposed that targeting liver cancer stem cells and chemotherapeutic drugs have a better selected, overall survival rate for hepatocellular carcinoma patients.
Aim
This study aims to investigate the effectiveness of targeting stem cells for liver cancer using a therapy that targets EpCAM in combination with chemotherapy and how this approach can enhance the treatment outcomes in hepatocellular carcinoma, the most prevalent kind of liver cancer.
Results
The outcome was studied by flow cytometry, Western blot, RT-PCR, and cytotoxicity assays. EpCAM gene silenced and XAV939-treated cells showed decreased expression of CD133, a liver cancer stem cell (LCSC) marker in flow cytometry analysis, and reduced expression of ABCG2 gene, which is a reliable marker for chemoresistance in RT-PCR and western blot analysis; it was also unable to form colonies in colony forming assay. Similarly, in the spheroid formation assay, EpCAM gene silenced cells and XAV939-treated cells in combinations with cisplatin treatment were powerless to appear spheroid, whereas cisplatin alone-treated cells showed spheroids. In the cytotoxicity assay, cisplatin alone and combined with EpCAM silenced and XAV939-treated cells showed more lactate dehydrogenase (LDH) release than EpCAM silenced arm XAV939 treated components.
Conclusion
These findings confirm our hypothesis that conventional chemotherapy kills cancer cells but not cancer stem cells. We believe EpCAM-targeted therapy enhances chemosensitivity and decreases relapsed chances. This approach might be the best option for a better prognosis for hepatocellular carcinoma patients.</description><identifier>ISSN: 2090-6226</identifier><identifier>ISSN: 2090-6218</identifier><identifier>EISSN: 2090-6226</identifier><identifier>DOI: 10.1186/s43066-023-00263-x</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Analysis ; Cancer ; Cancer stem cell ; Cancer therapies ; Cell culture ; Chemotherapy ; Cloning ; Development and progression ; Drug resistance in microorganisms ; Drugs ; EpCAM ; Epidemiology ; Ethylenediaminetetraacetic acid ; Flow cytometry ; Genetic engineering ; Health aspects ; Hepatocellular ; Hepatology ; Hepatoma ; Liver cancer ; Liver cirrhosis ; Medical research ; Medicine ; Medicine & Public Health ; Metastasis ; Microbiology ; Monoclonal antibodies ; Original Research Article ; Pathology ; Radiation therapy ; Reagents ; Statistical analysis ; Stem cell research ; Stem cells ; Transplantation ; Virology ; Wnt-β catenin ; XAV939</subject><ispartof>Egyptian Liver Journal, 2023-12, Vol.13 (1), p.29-9, Article 29</ispartof><rights>The Author(s) 2023</rights><rights>COPYRIGHT 2023 Springer</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-d08d4ece5b21ccb7d3fb8b2fdcdc3a251aa1734ae2025b0936c0e49eebe5abc33</citedby><cites>FETCH-LOGICAL-c496t-d08d4ece5b21ccb7d3fb8b2fdcdc3a251aa1734ae2025b0936c0e49eebe5abc33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>Sekar, Vasanthakumar</creatorcontrib><creatorcontrib>Veerabathiran, Ramakrishnan</creatorcontrib><creatorcontrib>Pandian, Arjun</creatorcontrib><creatorcontrib>Sivamani, Ganesan</creatorcontrib><title>Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma</title><title>Egyptian Liver Journal</title><addtitle>Egypt Liver Journal</addtitle><description>Background
Two chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors such as hypoxia, cancer stem cells, and drug efflux mechanism cancer stem cells (CSC) which are significant factors involved in chemoresistance. It has been exposed that targeting liver cancer stem cells and chemotherapeutic drugs have a better selected, overall survival rate for hepatocellular carcinoma patients.
Aim
This study aims to investigate the effectiveness of targeting stem cells for liver cancer using a therapy that targets EpCAM in combination with chemotherapy and how this approach can enhance the treatment outcomes in hepatocellular carcinoma, the most prevalent kind of liver cancer.
Results
The outcome was studied by flow cytometry, Western blot, RT-PCR, and cytotoxicity assays. EpCAM gene silenced and XAV939-treated cells showed decreased expression of CD133, a liver cancer stem cell (LCSC) marker in flow cytometry analysis, and reduced expression of ABCG2 gene, which is a reliable marker for chemoresistance in RT-PCR and western blot analysis; it was also unable to form colonies in colony forming assay. Similarly, in the spheroid formation assay, EpCAM gene silenced cells and XAV939-treated cells in combinations with cisplatin treatment were powerless to appear spheroid, whereas cisplatin alone-treated cells showed spheroids. In the cytotoxicity assay, cisplatin alone and combined with EpCAM silenced and XAV939-treated cells showed more lactate dehydrogenase (LDH) release than EpCAM silenced arm XAV939 treated components.
Conclusion
These findings confirm our hypothesis that conventional chemotherapy kills cancer cells but not cancer stem cells. We believe EpCAM-targeted therapy enhances chemosensitivity and decreases relapsed chances. This approach might be the best option for a better prognosis for hepatocellular carcinoma patients.</description><subject>Analysis</subject><subject>Cancer</subject><subject>Cancer stem cell</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Chemotherapy</subject><subject>Cloning</subject><subject>Development and progression</subject><subject>Drug resistance in microorganisms</subject><subject>Drugs</subject><subject>EpCAM</subject><subject>Epidemiology</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Flow cytometry</subject><subject>Genetic engineering</subject><subject>Health aspects</subject><subject>Hepatocellular</subject><subject>Hepatology</subject><subject>Hepatoma</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastasis</subject><subject>Microbiology</subject><subject>Monoclonal antibodies</subject><subject>Original Research Article</subject><subject>Pathology</subject><subject>Radiation therapy</subject><subject>Reagents</subject><subject>Statistical analysis</subject><subject>Stem cell research</subject><subject>Stem cells</subject><subject>Transplantation</subject><subject>Virology</subject><subject>Wnt-β catenin</subject><subject>XAV939</subject><issn>2090-6226</issn><issn>2090-6218</issn><issn>2090-6226</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9Uk1v1DAQjRBIVNv-AU6WOKf4I3Gc42pVoFIRl3K2_DFJvErsYHuh_Qv8ary7QIuEsA8zHr_3ZkZ6VfWG4GtCBH-XGoY5rzFlNcaUs_rhRXVBcY9rTil_-Sx_XV2ltMflCNJh1l1UP-5VHCE7P6LZfYOIjPKmhJRhQQbmGeUphsM4oZt1t_1UXhDV-ojyiQYWfXd5QmaCJfz-Am9DTFDidNSyaI1hjJCSCx45jyZYVQ5H7cOsjg2jcT4s6rJ6Nag5wdWvuKm-vL-5332s7z5_uN1t72rT9DzXFgvbgIFWU2KM7iwbtNB0sMYapmhLlCIdaxRQTFuNe8YNhqYH0NAqbRjbVLdnXRvUXq7RLSo-yqCcPBVCHKWK2ZkZJMGdboRgQgvcsNb0gja0GTjpNWNdq4rW27NW2fHrAVKW-3CIvowvqaAdxn1L2ifUqIqo80PIUZnFJSO3Xcsop6w02VTX_0CVa2FxJngYXKn_RaBngokhpQjDn2UIlkdnyLMzZHGGPDlDPhQSO5NSAfsR4tPE_2H9BI2bvWE</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Sekar, Vasanthakumar</creator><creator>Veerabathiran, Ramakrishnan</creator><creator>Pandian, Arjun</creator><creator>Sivamani, Ganesan</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><general>SpringerOpen</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>DOA</scope></search><sort><creationdate>20231201</creationdate><title>Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma</title><author>Sekar, Vasanthakumar ; Veerabathiran, Ramakrishnan ; Pandian, Arjun ; Sivamani, Ganesan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-d08d4ece5b21ccb7d3fb8b2fdcdc3a251aa1734ae2025b0936c0e49eebe5abc33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Cancer</topic><topic>Cancer stem cell</topic><topic>Cancer therapies</topic><topic>Cell culture</topic><topic>Chemotherapy</topic><topic>Cloning</topic><topic>Development and progression</topic><topic>Drug resistance in microorganisms</topic><topic>Drugs</topic><topic>EpCAM</topic><topic>Epidemiology</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Flow cytometry</topic><topic>Genetic engineering</topic><topic>Health aspects</topic><topic>Hepatocellular</topic><topic>Hepatology</topic><topic>Hepatoma</topic><topic>Liver cancer</topic><topic>Liver cirrhosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastasis</topic><topic>Microbiology</topic><topic>Monoclonal antibodies</topic><topic>Original Research Article</topic><topic>Pathology</topic><topic>Radiation therapy</topic><topic>Reagents</topic><topic>Statistical analysis</topic><topic>Stem cell research</topic><topic>Stem cells</topic><topic>Transplantation</topic><topic>Virology</topic><topic>Wnt-β catenin</topic><topic>XAV939</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sekar, Vasanthakumar</creatorcontrib><creatorcontrib>Veerabathiran, Ramakrishnan</creatorcontrib><creatorcontrib>Pandian, Arjun</creatorcontrib><creatorcontrib>Sivamani, Ganesan</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</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>DOAJ Directory of Open Access Journals</collection><jtitle>Egyptian Liver Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sekar, Vasanthakumar</au><au>Veerabathiran, Ramakrishnan</au><au>Pandian, Arjun</au><au>Sivamani, Ganesan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma</atitle><jtitle>Egyptian Liver Journal</jtitle><stitle>Egypt Liver Journal</stitle><date>2023-12-01</date><risdate>2023</risdate><volume>13</volume><issue>1</issue><spage>29</spage><epage>9</epage><pages>29-9</pages><artnum>29</artnum><issn>2090-6226</issn><issn>2090-6218</issn><eissn>2090-6226</eissn><abstract>Background
Two chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors such as hypoxia, cancer stem cells, and drug efflux mechanism cancer stem cells (CSC) which are significant factors involved in chemoresistance. It has been exposed that targeting liver cancer stem cells and chemotherapeutic drugs have a better selected, overall survival rate for hepatocellular carcinoma patients.
Aim
This study aims to investigate the effectiveness of targeting stem cells for liver cancer using a therapy that targets EpCAM in combination with chemotherapy and how this approach can enhance the treatment outcomes in hepatocellular carcinoma, the most prevalent kind of liver cancer.
Results
The outcome was studied by flow cytometry, Western blot, RT-PCR, and cytotoxicity assays. EpCAM gene silenced and XAV939-treated cells showed decreased expression of CD133, a liver cancer stem cell (LCSC) marker in flow cytometry analysis, and reduced expression of ABCG2 gene, which is a reliable marker for chemoresistance in RT-PCR and western blot analysis; it was also unable to form colonies in colony forming assay. Similarly, in the spheroid formation assay, EpCAM gene silenced cells and XAV939-treated cells in combinations with cisplatin treatment were powerless to appear spheroid, whereas cisplatin alone-treated cells showed spheroids. In the cytotoxicity assay, cisplatin alone and combined with EpCAM silenced and XAV939-treated cells showed more lactate dehydrogenase (LDH) release than EpCAM silenced arm XAV939 treated components.
Conclusion
These findings confirm our hypothesis that conventional chemotherapy kills cancer cells but not cancer stem cells. We believe EpCAM-targeted therapy enhances chemosensitivity and decreases relapsed chances. This approach might be the best option for a better prognosis for hepatocellular carcinoma patients.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><doi>10.1186/s43066-023-00263-x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Cancer Cancer stem cell Cancer therapies Cell culture Chemotherapy Cloning Development and progression Drug resistance in microorganisms Drugs EpCAM Epidemiology Ethylenediaminetetraacetic acid Flow cytometry Genetic engineering Health aspects Hepatocellular Hepatology Hepatoma Liver cancer Liver cirrhosis Medical research Medicine Medicine & Public Health Metastasis Microbiology Monoclonal antibodies Original Research Article Pathology Radiation therapy Reagents Statistical analysis Stem cell research Stem cells Transplantation Virology Wnt-β catenin XAV939 |
| title | Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma |
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