Metabolic alteration – Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics
Abstract Background and Objectives It can be assumed that PGK1 is involved in metastatic spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of consid...
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| Veröffentlicht in: | International journal of surgery (London, England) England), 2015-10, Vol.22, p.92-98 |
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| creator | Schneider, Carl Christoph Archid, Rami Fischer, Nathania Bühler, Sarah Venturelli, Sascha Berger, Alexander Burkard, Markus Kirschniak, Andreas Bachmann, Robert Königsrainer, Alfred Glatzle, Jörg Zieker, Derek |
| description | Abstract Background and Objectives It can be assumed that PGK1 is involved in metastatic spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of considerable importance. We hypothesized that inhibition of PGK1 makes these cells more sensitive to chemotherapeutic agents and therefore mediates an overcome of the existing therapy resistance. Methods All investigations were performed with human gastric adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus-shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and mitomycin. FACS, qRT-PCR, and xCELLigence were performed. Results Using the medium-sole-control indicating the highest cell viability and Triton indicating the lowest, mitomycin and 5-FU alone showed a significant decrease in cell viability. The treatment with AdvshPGK1 alone already showed a better decrease. The simultaneous application of chemotherapeutics and adenovirus showed the strongest effect and is comparable to the effect of Triton. Conclusions We showed a significant decrease in cell viability after the simultaneous application of chemotherapeutics and adenovirus. These results suggest that PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells to overcome the chemotherapeutic therapy resistance. |
| doi_str_mv | 10.1016/j.ijsu.2015.08.020 |
| format | Article |
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Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of considerable importance. We hypothesized that inhibition of PGK1 makes these cells more sensitive to chemotherapeutic agents and therefore mediates an overcome of the existing therapy resistance. Methods All investigations were performed with human gastric adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus-shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and mitomycin. FACS, qRT-PCR, and xCELLigence were performed. Results Using the medium-sole-control indicating the highest cell viability and Triton indicating the lowest, mitomycin and 5-FU alone showed a significant decrease in cell viability. The treatment with AdvshPGK1 alone already showed a better decrease. The simultaneous application of chemotherapeutics and adenovirus showed the strongest effect and is comparable to the effect of Triton. Conclusions We showed a significant decrease in cell viability after the simultaneous application of chemotherapeutics and adenovirus. These results suggest that PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells to overcome the chemotherapeutic therapy resistance.</description><identifier>ISSN: 1743-9191</identifier><identifier>EISSN: 1743-9159</identifier><identifier>DOI: 10.1016/j.ijsu.2015.08.020</identifier><identifier>PMID: 26298000</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Adenoviridae ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cell Line, Tumor ; Combined in vitro therapy chemotherapeutics and adenovirus anti-PGK1 ; Drug Resistance, Neoplasm ; Fluorouracil - administration & dosage ; Human gastric adenocarcinoma cell line 23132/87 ; Humans ; Metabolic alteration ; Mitomycin - administration & dosage ; Neoplasm Metastasis ; PGK1 ; PGK1-inhibition ; Phosphoglycerate Kinase - antagonists & inhibitors ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology ; Surgery ; Therapy resistance in gastric cancer</subject><ispartof>International journal of surgery (London, England), 2015-10, Vol.22, p.92-98</ispartof><rights>IJS Publishing Group Limited</rights><rights>2015 IJS Publishing Group Limited</rights><rights>Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-2f52a5e23b389a9c6ca9da059f3646c85c1dd077efb1ec0bb245fcffce908e623</citedby><cites>FETCH-LOGICAL-c455t-2f52a5e23b389a9c6ca9da059f3646c85c1dd077efb1ec0bb245fcffce908e623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijsu.2015.08.020$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26298000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schneider, Carl Christoph</creatorcontrib><creatorcontrib>Archid, Rami</creatorcontrib><creatorcontrib>Fischer, Nathania</creatorcontrib><creatorcontrib>Bühler, Sarah</creatorcontrib><creatorcontrib>Venturelli, Sascha</creatorcontrib><creatorcontrib>Berger, Alexander</creatorcontrib><creatorcontrib>Burkard, Markus</creatorcontrib><creatorcontrib>Kirschniak, Andreas</creatorcontrib><creatorcontrib>Bachmann, Robert</creatorcontrib><creatorcontrib>Königsrainer, Alfred</creatorcontrib><creatorcontrib>Glatzle, Jörg</creatorcontrib><creatorcontrib>Zieker, Derek</creatorcontrib><title>Metabolic alteration – Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics</title><title>International journal of surgery (London, England)</title><addtitle>Int J Surg</addtitle><description>Abstract Background and Objectives It can be assumed that PGK1 is involved in metastatic spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of considerable importance. We hypothesized that inhibition of PGK1 makes these cells more sensitive to chemotherapeutic agents and therefore mediates an overcome of the existing therapy resistance. Methods All investigations were performed with human gastric adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus-shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and mitomycin. FACS, qRT-PCR, and xCELLigence were performed. Results Using the medium-sole-control indicating the highest cell viability and Triton indicating the lowest, mitomycin and 5-FU alone showed a significant decrease in cell viability. The treatment with AdvshPGK1 alone already showed a better decrease. The simultaneous application of chemotherapeutics and adenovirus showed the strongest effect and is comparable to the effect of Triton. Conclusions We showed a significant decrease in cell viability after the simultaneous application of chemotherapeutics and adenovirus. These results suggest that PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells to overcome the chemotherapeutic therapy resistance.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenoviridae</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Combined in vitro therapy chemotherapeutics and adenovirus anti-PGK1</subject><subject>Drug Resistance, Neoplasm</subject><subject>Fluorouracil - administration & dosage</subject><subject>Human gastric adenocarcinoma cell line 23132/87</subject><subject>Humans</subject><subject>Metabolic alteration</subject><subject>Mitomycin - administration & dosage</subject><subject>Neoplasm Metastasis</subject><subject>PGK1</subject><subject>PGK1-inhibition</subject><subject>Phosphoglycerate Kinase - antagonists & inhibitors</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><subject>Surgery</subject><subject>Therapy resistance in gastric cancer</subject><issn>1743-9191</issn><issn>1743-9159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ks1u1DAUhSMEoqXwAiyQl2wSbCdOYgkhoQoKoqhIgMTOcm5uOjfkZ2o7g2bHO_QNeRIcpsyCBStbPud8ku-5SfJU8ExwUb7oM-r9kkkuVMbrjEt-LzkVVZGnWih9_3jX4iR55H3PecFrUT9MTmQpdc05P01uP2KwzTwQMDsEdDbQPLFfP2_Z1Q4dzCNN1yxsorDdM4eefLATIKOJXVsfXMzB-uDYjiz7dPEhFVHbUEN_QNFmWaQ0NGF75PygsGErqLWuZbDBcT5IuAQC_zh50NnB45O78yz5-vbNl_N36eXVxfvz15cpFEqFVHZKWoUyb_JaWw0lWN1arnSXl0UJtQLRtryqsGsEAm8aWagOug5Q8xpLmZ8lzw_crZtvFvTBjOQBh8FOOC_eiEpKUVeyyqNVHqzgZu8ddmbraLRubwQ3axmmN2sZZi3D8NrEMmLo2R1_aUZsj5G_04-GlwcDxl_uCJ3xQBin2ZJDCKad6f_8V__EYaCJwA7fcY--nxc3xfkZYbw03Hxe12HdBqG4EEJ_y38DfaO0pw</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Schneider, Carl Christoph</creator><creator>Archid, Rami</creator><creator>Fischer, Nathania</creator><creator>Bühler, Sarah</creator><creator>Venturelli, Sascha</creator><creator>Berger, Alexander</creator><creator>Burkard, Markus</creator><creator>Kirschniak, Andreas</creator><creator>Bachmann, Robert</creator><creator>Königsrainer, Alfred</creator><creator>Glatzle, Jörg</creator><creator>Zieker, Derek</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><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></search><sort><creationdate>20151001</creationdate><title>Metabolic alteration – Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics</title><author>Schneider, Carl Christoph ; Archid, Rami ; Fischer, Nathania ; Bühler, Sarah ; Venturelli, Sascha ; Berger, Alexander ; Burkard, Markus ; Kirschniak, Andreas ; Bachmann, Robert ; Königsrainer, Alfred ; Glatzle, Jörg ; Zieker, Derek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-2f52a5e23b389a9c6ca9da059f3646c85c1dd077efb1ec0bb245fcffce908e623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenoviridae</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Combined in vitro therapy chemotherapeutics and adenovirus anti-PGK1</topic><topic>Drug Resistance, Neoplasm</topic><topic>Fluorouracil - administration & dosage</topic><topic>Human gastric adenocarcinoma cell line 23132/87</topic><topic>Humans</topic><topic>Metabolic alteration</topic><topic>Mitomycin - administration & dosage</topic><topic>Neoplasm Metastasis</topic><topic>PGK1</topic><topic>PGK1-inhibition</topic><topic>Phosphoglycerate Kinase - antagonists & inhibitors</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><topic>Surgery</topic><topic>Therapy resistance in gastric cancer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schneider, Carl Christoph</creatorcontrib><creatorcontrib>Archid, Rami</creatorcontrib><creatorcontrib>Fischer, Nathania</creatorcontrib><creatorcontrib>Bühler, Sarah</creatorcontrib><creatorcontrib>Venturelli, Sascha</creatorcontrib><creatorcontrib>Berger, Alexander</creatorcontrib><creatorcontrib>Burkard, Markus</creatorcontrib><creatorcontrib>Kirschniak, Andreas</creatorcontrib><creatorcontrib>Bachmann, Robert</creatorcontrib><creatorcontrib>Königsrainer, Alfred</creatorcontrib><creatorcontrib>Glatzle, Jörg</creatorcontrib><creatorcontrib>Zieker, Derek</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect: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>MEDLINE - Academic</collection><jtitle>International journal of surgery (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schneider, Carl Christoph</au><au>Archid, Rami</au><au>Fischer, Nathania</au><au>Bühler, Sarah</au><au>Venturelli, Sascha</au><au>Berger, Alexander</au><au>Burkard, Markus</au><au>Kirschniak, Andreas</au><au>Bachmann, Robert</au><au>Königsrainer, Alfred</au><au>Glatzle, Jörg</au><au>Zieker, Derek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic alteration – Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics</atitle><jtitle>International journal of surgery (London, England)</jtitle><addtitle>Int J Surg</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>22</volume><spage>92</spage><epage>98</epage><pages>92-98</pages><issn>1743-9191</issn><eissn>1743-9159</eissn><abstract>Abstract Background and Objectives It can be assumed that PGK1 is involved in metastatic spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of considerable importance. We hypothesized that inhibition of PGK1 makes these cells more sensitive to chemotherapeutic agents and therefore mediates an overcome of the existing therapy resistance. Methods All investigations were performed with human gastric adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus-shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and mitomycin. FACS, qRT-PCR, and xCELLigence were performed. Results Using the medium-sole-control indicating the highest cell viability and Triton indicating the lowest, mitomycin and 5-FU alone showed a significant decrease in cell viability. The treatment with AdvshPGK1 alone already showed a better decrease. The simultaneous application of chemotherapeutics and adenovirus showed the strongest effect and is comparable to the effect of Triton. Conclusions We showed a significant decrease in cell viability after the simultaneous application of chemotherapeutics and adenovirus. These results suggest that PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells to overcome the chemotherapeutic therapy resistance.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26298000</pmid><doi>10.1016/j.ijsu.2015.08.020</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenoviridae Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cell Line, Tumor Combined in vitro therapy chemotherapeutics and adenovirus anti-PGK1 Drug Resistance, Neoplasm Fluorouracil - administration & dosage Human gastric adenocarcinoma cell line 23132/87 Humans Metabolic alteration Mitomycin - administration & dosage Neoplasm Metastasis PGK1 PGK1-inhibition Phosphoglycerate Kinase - antagonists & inhibitors Stomach Neoplasms - drug therapy Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Surgery Therapy resistance in gastric cancer |
| title | Metabolic alteration – Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics |
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