Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts
Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carci...
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| creator | Cao, Long-Hui Li, Hui-Ting Lin, Wen-Qian Tan, Hong-Ying Xie, Lan Zhong, Zhong-Jian Zhou, Jian-Hua |
| description | Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 μg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 μg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an
in vivo
nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models
in vitro
and
in vivo
by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. |
| doi_str_mv | 10.1038/srep18706 |
| format | Article |
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in vivo
nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models
in vitro
and
in vivo
by inhibiting cisplatin-induced apoptosis and decreasing neovascularization.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep18706</identifier><identifier>PMID: 26729257</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/2 ; 13/51 ; 692/308/409 ; 692/700/565/1436/1437 ; 692/700/565/1436/99 ; Analgesics ; Animal models ; Animals ; Antineoplastic Agents - pharmacology ; Antitumor activity ; Apoptosis ; Apoptosis - drug effects ; Bcl protein ; Bcl-2 protein ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Carcinoma ; Caspase ; Caspase-3 ; Caspases - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Chemoresistance ; Cisplatin ; Cisplatin - pharmacology ; Cytotoxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Antagonism ; Gene Expression ; Humanities and Social Sciences ; Humans ; Metastases ; Mice ; Mice, Nude ; Morphine ; Morphine - pharmacology ; multidisciplinary ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms - drug therapy ; Nasopharyngeal Neoplasms - metabolism ; Nasopharyngeal Neoplasms - pathology ; Opioids ; Pain ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Science ; Throat cancer ; Tumor Burden ; Vascularization ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>Scientific reports, 2016-01, Vol.6 (1), p.18706-18706, Article 18706</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jan 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-239ac89e4c245e1abcde24430ade02d895681faf389f0db7730bcee428f363b43</citedby><cites>FETCH-LOGICAL-c504t-239ac89e4c245e1abcde24430ade02d895681faf389f0db7730bcee428f363b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700493/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700493/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26729257$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Long-Hui</creatorcontrib><creatorcontrib>Li, Hui-Ting</creatorcontrib><creatorcontrib>Lin, Wen-Qian</creatorcontrib><creatorcontrib>Tan, Hong-Ying</creatorcontrib><creatorcontrib>Xie, Lan</creatorcontrib><creatorcontrib>Zhong, Zhong-Jian</creatorcontrib><creatorcontrib>Zhou, Jian-Hua</creatorcontrib><title>Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 μg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 μg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an
in vivo
nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models
in vitro
and
in vivo
by inhibiting cisplatin-induced apoptosis and decreasing neovascularization.</description><subject>13</subject><subject>13/2</subject><subject>13/51</subject><subject>692/308/409</subject><subject>692/700/565/1436/1437</subject><subject>692/700/565/1436/99</subject><subject>Analgesics</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bcl protein</subject><subject>Bcl-2 protein</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Carcinoma</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Caspases - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chemoresistance</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Antagonism</subject><subject>Gene Expression</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>multidisciplinary</subject><subject>Nasopharyngeal Carcinoma</subject><subject>Nasopharyngeal Neoplasms - drug therapy</subject><subject>Nasopharyngeal Neoplasms - metabolism</subject><subject>Nasopharyngeal Neoplasms - pathology</subject><subject>Opioids</subject><subject>Pain</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Science</subject><subject>Throat cancer</subject><subject>Tumor Burden</subject><subject>Vascularization</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkk1v1DAQhiMEolXpgT-ALHEB1AXHcTbxBQlVfElFXOBsTRwncZV4jMeB7i_ib-Jqy7KAL2NpHr3zzkdRPC75y5JX7SuKNpRtw7f3ilPBZb0RlRD3j_4nxTnRNc-vFkqW6mFxIraNUKJuToufnzCGyXl7wYAFTNYnBzMDn2BE7ygxHJhxFGZIzjOzS5jwxhmXdhfM-cl1LtEfYON8vxrbMwgYEpKjLNUzWkOIlsihv9VL64KRjRF_pCmLMA-EYYK486PNxQ1E4zwuwG6sxzHCkOhR8WCAmez5XTwrvr57--Xyw-bq8_uPl2-uNqbmMuV-FZhWWWmErG0JnemtkLLi0Fsu-lbV27YcYKhaNfC-a5qKd8ZaKdqh2ladrM6K13vdsHaL7U2eR4RZh-iW7E8jOP13xrtJj_hdy4Zzqaos8OxOIOK31VLSiyNj5xm8xZV02dSSt1suRUaf_oNe4xp9bk-XrVIZyb4y9XxPmYiUlz0czJRc316APlxAZp8cuz-Qv_edgRd7gHIqTzselfxP7RddOMDe</recordid><startdate>20160105</startdate><enddate>20160105</enddate><creator>Cao, Long-Hui</creator><creator>Li, Hui-Ting</creator><creator>Lin, Wen-Qian</creator><creator>Tan, Hong-Ying</creator><creator>Xie, Lan</creator><creator>Zhong, Zhong-Jian</creator><creator>Zhou, Jian-Hua</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160105</creationdate><title>Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts</title><author>Cao, Long-Hui ; Li, Hui-Ting ; Lin, Wen-Qian ; Tan, Hong-Ying ; Xie, Lan ; Zhong, Zhong-Jian ; Zhou, Jian-Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-239ac89e4c245e1abcde24430ade02d895681faf389f0db7730bcee428f363b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13</topic><topic>13/2</topic><topic>13/51</topic><topic>692/308/409</topic><topic>692/700/565/1436/1437</topic><topic>692/700/565/1436/99</topic><topic>Analgesics</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bcl protein</topic><topic>Bcl-2 protein</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Carcinoma</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Caspases - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Chemoresistance</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Cytotoxicity</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Antagonism</topic><topic>Gene Expression</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>multidisciplinary</topic><topic>Nasopharyngeal Carcinoma</topic><topic>Nasopharyngeal Neoplasms - drug therapy</topic><topic>Nasopharyngeal Neoplasms - metabolism</topic><topic>Nasopharyngeal Neoplasms - pathology</topic><topic>Opioids</topic><topic>Pain</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Science</topic><topic>Throat cancer</topic><topic>Tumor Burden</topic><topic>Vascularization</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Long-Hui</creatorcontrib><creatorcontrib>Li, Hui-Ting</creatorcontrib><creatorcontrib>Lin, Wen-Qian</creatorcontrib><creatorcontrib>Tan, Hong-Ying</creatorcontrib><creatorcontrib>Xie, Lan</creatorcontrib><creatorcontrib>Zhong, Zhong-Jian</creatorcontrib><creatorcontrib>Zhou, Jian-Hua</creatorcontrib><collection>Springer Nature OA Free Journals</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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 Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Long-Hui</au><au>Li, Hui-Ting</au><au>Lin, Wen-Qian</au><au>Tan, Hong-Ying</au><au>Xie, Lan</au><au>Zhong, Zhong-Jian</au><au>Zhou, Jian-Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-01-05</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>18706</spage><epage>18706</epage><pages>18706-18706</pages><artnum>18706</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 μg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 μg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an
in vivo
nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models
in vitro
and
in vivo
by inhibiting cisplatin-induced apoptosis and decreasing neovascularization.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26729257</pmid><doi>10.1038/srep18706</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 13 13/2 13/51 692/308/409 692/700/565/1436/1437 692/700/565/1436/99 Analgesics Animal models Animals Antineoplastic Agents - pharmacology Antitumor activity Apoptosis Apoptosis - drug effects Bcl protein Bcl-2 protein bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Carcinoma Caspase Caspase-3 Caspases - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Chemoresistance Cisplatin Cisplatin - pharmacology Cytotoxicity Disease Models, Animal Dose-Response Relationship, Drug Drug Antagonism Gene Expression Humanities and Social Sciences Humans Metastases Mice Mice, Nude Morphine Morphine - pharmacology multidisciplinary Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms - drug therapy Nasopharyngeal Neoplasms - metabolism Nasopharyngeal Neoplasms - pathology Opioids Pain Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Science Throat cancer Tumor Burden Vascularization Xenograft Model Antitumor Assays Xenografts |
| title | Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts |
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