Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer
Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colore...
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| creator | de Heer, Pieter Sandel, Maro H. Guertens, Gunther de Boeck, Gert Koudijs, Margaretha M. Nagelkerke, J. Fred Junggeburt, Jan M. C. de Bruijn, Ernst A. van de Velde, Cornelis J. H. Kuppen, Peter J. K. |
| description | Introduction
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.
Materials and methods
The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE
2
and celecoxib levels were determined.
Results
CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 μg/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 μg/ml were needed to affect tumor cell viability.
Conclusion
These results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth. |
| doi_str_mv | 10.1007/s00280-007-0668-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2516537</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1536964181</sourcerecordid><originalsourceid>FETCH-LOGICAL-c497t-2fee8d7ac9f33461e6442b48a030d5d08c80b52141250505d4a8e90a5a734adb3</originalsourceid><addsrcrecordid>eNp1kU2LFDEQhoMo7rj6A7xIEPTWWkkq_XERZNhVYcGLnkM6XT2TJd1Zk-7V_fdmmGFXBUkgBfXUW1V5GXsp4J0AaN5nANlCVcIK6rqt8BHbCFSyghbVY7YBhVjpBvCMPcv5GgBQKPWUnYlWYgOy2zC3pUAu_vI99_Pe937JfJfiz2XP48iXdYoplwy3PN_NO5rJO57swoO_pcQnWmwulzKf4kCBjzFxF0NM5BYbuLOzo_ScPRltyPTi9J6z75cX37afq6uvn75sP15VDrtmqeRI1A6Ndd2oFNaCakTZY2tBwaAHaF0LvZYChdRQzoC2pQ6sto1CO_TqnH046t6s_USDo3lJNpib5Ceb7ky03vydmf3e7OKtkVrUWjVF4O1JIMUfK-XFTD47CsHOFNds6g5lp1so4Ot_wOu4prksZ6RQqDrUWCBxhFyKOSca7ycRYA7-maN_5hAe_DOHmld_rvBQcTKsAG9OgM3OhjGVH_b5npNQS-gaXTh55HJJFePSw4T_7_4bRD-z1A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>213439454</pqid></control><display><type>article</type><title>Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>de Heer, Pieter ; Sandel, Maro H. ; Guertens, Gunther ; de Boeck, Gert ; Koudijs, Margaretha M. ; Nagelkerke, J. Fred ; Junggeburt, Jan M. C. ; de Bruijn, Ernst A. ; van de Velde, Cornelis J. H. ; Kuppen, Peter J. K.</creator><creatorcontrib>de Heer, Pieter ; Sandel, Maro H. ; Guertens, Gunther ; de Boeck, Gert ; Koudijs, Margaretha M. ; Nagelkerke, J. Fred ; Junggeburt, Jan M. C. ; de Bruijn, Ernst A. ; van de Velde, Cornelis J. H. ; Kuppen, Peter J. K.</creatorcontrib><description>Introduction
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.
Materials and methods
The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE
2
and celecoxib levels were determined.
Results
CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 μg/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 μg/ml were needed to affect tumor cell viability.
Conclusion
These results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-007-0668-4</identifier><identifier>PMID: 18247029</identifier><identifier>CODEN: CCPHDZ</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - secondary ; Animals ; Antineoplastic Agents ; Apoptosis - drug effects ; Biological and medical sciences ; Cancer Research ; Caspase 3 - metabolism ; Celecoxib ; Cell Survival - drug effects ; Colorectal cancer ; Colorectal Neoplasms - pathology ; Cyclooxygenase 2 Inhibitors - blood ; Cyclooxygenase 2 Inhibitors - pharmacology ; Dinoprostone - blood ; Dinoprostone - metabolism ; Gastroenterology. Liver. Pancreas. Abdomen ; Immunohistochemistry ; Killer Cells, Natural - immunology ; Liver Neoplasms - drug therapy ; Liver Neoplasms - secondary ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Neoplasm Metastasis ; Neoplasm Transplantation ; Neutrophil Infiltration - drug effects ; Oncology ; Original ; Original Article ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Prostaglandins - biosynthesis ; Pyrazoles - blood ; Pyrazoles - pharmacology ; Rats ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Sulfonamides - blood ; Sulfonamides - pharmacology ; T-Lymphocytes - immunology ; Tumors</subject><ispartof>Cancer chemotherapy and pharmacology, 2008-10, Vol.62 (5), p.811-819</ispartof><rights>The Author(s) 2008</rights><rights>2008 INIST-CNRS</rights><rights>Springer-Verlag 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-2fee8d7ac9f33461e6442b48a030d5d08c80b52141250505d4a8e90a5a734adb3</citedby><cites>FETCH-LOGICAL-c497t-2fee8d7ac9f33461e6442b48a030d5d08c80b52141250505d4a8e90a5a734adb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00280-007-0668-4$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00280-007-0668-4$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20620975$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18247029$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Heer, Pieter</creatorcontrib><creatorcontrib>Sandel, Maro H.</creatorcontrib><creatorcontrib>Guertens, Gunther</creatorcontrib><creatorcontrib>de Boeck, Gert</creatorcontrib><creatorcontrib>Koudijs, Margaretha M.</creatorcontrib><creatorcontrib>Nagelkerke, J. Fred</creatorcontrib><creatorcontrib>Junggeburt, Jan M. C.</creatorcontrib><creatorcontrib>de Bruijn, Ernst A.</creatorcontrib><creatorcontrib>van de Velde, Cornelis J. H.</creatorcontrib><creatorcontrib>Kuppen, Peter J. K.</creatorcontrib><title>Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Introduction
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.
Materials and methods
The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE
2
and celecoxib levels were determined.
Results
CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 μg/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 μg/ml were needed to affect tumor cell viability.
Conclusion
These results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - secondary</subject><subject>Animals</subject><subject>Antineoplastic Agents</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cancer Research</subject><subject>Caspase 3 - metabolism</subject><subject>Celecoxib</subject><subject>Cell Survival - drug effects</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Cyclooxygenase 2 Inhibitors - blood</subject><subject>Cyclooxygenase 2 Inhibitors - pharmacology</subject><subject>Dinoprostone - blood</subject><subject>Dinoprostone - metabolism</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Immunohistochemistry</subject><subject>Killer Cells, Natural - immunology</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - secondary</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Transplantation</subject><subject>Neutrophil Infiltration - drug effects</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Prostaglandins - biosynthesis</subject><subject>Pyrazoles - blood</subject><subject>Pyrazoles - pharmacology</subject><subject>Rats</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Sulfonamides - blood</subject><subject>Sulfonamides - pharmacology</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumors</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kU2LFDEQhoMo7rj6A7xIEPTWWkkq_XERZNhVYcGLnkM6XT2TJd1Zk-7V_fdmmGFXBUkgBfXUW1V5GXsp4J0AaN5nANlCVcIK6rqt8BHbCFSyghbVY7YBhVjpBvCMPcv5GgBQKPWUnYlWYgOy2zC3pUAu_vI99_Pe937JfJfiz2XP48iXdYoplwy3PN_NO5rJO57swoO_pcQnWmwulzKf4kCBjzFxF0NM5BYbuLOzo_ScPRltyPTi9J6z75cX37afq6uvn75sP15VDrtmqeRI1A6Ndd2oFNaCakTZY2tBwaAHaF0LvZYChdRQzoC2pQ6sto1CO_TqnH046t6s_USDo3lJNpib5Ceb7ky03vydmf3e7OKtkVrUWjVF4O1JIMUfK-XFTD47CsHOFNds6g5lp1so4Ot_wOu4prksZ6RQqDrUWCBxhFyKOSca7ycRYA7-maN_5hAe_DOHmld_rvBQcTKsAG9OgM3OhjGVH_b5npNQS-gaXTh55HJJFePSw4T_7_4bRD-z1A</recordid><startdate>20081001</startdate><enddate>20081001</enddate><creator>de Heer, Pieter</creator><creator>Sandel, Maro H.</creator><creator>Guertens, Gunther</creator><creator>de Boeck, Gert</creator><creator>Koudijs, Margaretha M.</creator><creator>Nagelkerke, J. Fred</creator><creator>Junggeburt, Jan M. C.</creator><creator>de Bruijn, Ernst A.</creator><creator>van de Velde, Cornelis J. H.</creator><creator>Kuppen, Peter J. K.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>IQODW</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081001</creationdate><title>Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer</title><author>de Heer, Pieter ; Sandel, Maro H. ; Guertens, Gunther ; de Boeck, Gert ; Koudijs, Margaretha M. ; Nagelkerke, J. Fred ; Junggeburt, Jan M. C. ; de Bruijn, Ernst A. ; van de Velde, Cornelis J. H. ; Kuppen, Peter J. K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-2fee8d7ac9f33461e6442b48a030d5d08c80b52141250505d4a8e90a5a734adb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - secondary</topic><topic>Animals</topic><topic>Antineoplastic Agents</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Cancer Research</topic><topic>Caspase 3 - metabolism</topic><topic>Celecoxib</topic><topic>Cell Survival - drug effects</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Cyclooxygenase 2 Inhibitors - blood</topic><topic>Cyclooxygenase 2 Inhibitors - pharmacology</topic><topic>Dinoprostone - blood</topic><topic>Dinoprostone - metabolism</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Immunohistochemistry</topic><topic>Killer Cells, Natural - immunology</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - secondary</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasm Transplantation</topic><topic>Neutrophil Infiltration - drug effects</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Prostaglandins - biosynthesis</topic><topic>Pyrazoles - blood</topic><topic>Pyrazoles - pharmacology</topic><topic>Rats</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Sulfonamides - blood</topic><topic>Sulfonamides - pharmacology</topic><topic>T-Lymphocytes - immunology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Heer, Pieter</creatorcontrib><creatorcontrib>Sandel, Maro H.</creatorcontrib><creatorcontrib>Guertens, Gunther</creatorcontrib><creatorcontrib>de Boeck, Gert</creatorcontrib><creatorcontrib>Koudijs, Margaretha M.</creatorcontrib><creatorcontrib>Nagelkerke, J. Fred</creatorcontrib><creatorcontrib>Junggeburt, Jan M. C.</creatorcontrib><creatorcontrib>de Bruijn, Ernst A.</creatorcontrib><creatorcontrib>van de Velde, Cornelis J. H.</creatorcontrib><creatorcontrib>Kuppen, Peter J. K.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Pascal-Francis</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>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Heer, Pieter</au><au>Sandel, Maro H.</au><au>Guertens, Gunther</au><au>de Boeck, Gert</au><au>Koudijs, Margaretha M.</au><au>Nagelkerke, J. Fred</au><au>Junggeburt, Jan M. C.</au><au>de Bruijn, Ernst A.</au><au>van de Velde, Cornelis J. H.</au><au>Kuppen, Peter J. K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2008-10-01</date><risdate>2008</risdate><volume>62</volume><issue>5</issue><spage>811</spage><epage>819</epage><pages>811-819</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><coden>CCPHDZ</coden><abstract>Introduction
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.
Materials and methods
The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE
2
and celecoxib levels were determined.
Results
CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 μg/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 μg/ml were needed to affect tumor cell viability.
Conclusion
These results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>18247029</pmid><doi>10.1007/s00280-007-0668-4</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer chemotherapy and pharmacology, 2008-10, Vol.62 (5), p.811-819 |
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| language | eng |
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| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - secondary Animals Antineoplastic Agents Apoptosis - drug effects Biological and medical sciences Cancer Research Caspase 3 - metabolism Celecoxib Cell Survival - drug effects Colorectal cancer Colorectal Neoplasms - pathology Cyclooxygenase 2 Inhibitors - blood Cyclooxygenase 2 Inhibitors - pharmacology Dinoprostone - blood Dinoprostone - metabolism Gastroenterology. Liver. Pancreas. Abdomen Immunohistochemistry Killer Cells, Natural - immunology Liver Neoplasms - drug therapy Liver Neoplasms - secondary Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Medicine Medicine & Public Health Neoplasm Metastasis Neoplasm Transplantation Neutrophil Infiltration - drug effects Oncology Original Original Article Pharmacology. Drug treatments Pharmacology/Toxicology Prostaglandins - biosynthesis Pyrazoles - blood Pyrazoles - pharmacology Rats Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Sulfonamides - blood Sulfonamides - pharmacology T-Lymphocytes - immunology Tumors |
| title | Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer |
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