Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo
AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53(r Ad-p53) combined with 5-fluorouracil(5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance.METHODS nude mice bearing human colon cancer SW480/5-FU(5-FU res...
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| Veröffentlicht in: | World journal of gastroenterology : WJG 2016-08, Vol.22 (32), p.7342-7352 |
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| container_title | World journal of gastroenterology : WJG |
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| creator | Xie, Qi Wu, Min-Yi Zhang, Ding-Xuan Yang, Yi-Ming Wang, Bao-Shuai Zhang, Jing Xu, Jin Zhong, Wei-De Hu, Jia-Ni |
| description | AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53(r Ad-p53) combined with 5-fluorouracil(5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance.METHODS nude mice bearing human colon cancer SW480/5-FU(5-FU resistant) were randomly assigned to four groups(n = 25 each): control group, 5-FU group, r Ad-p53 group, and r Ad-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C(PKC), permeability-glycoprotein(P-gp) and multidrug resistance-associated protein 1(MRP1)(Western blot) and apoptosis(TUNEL) were determined.RESULTS The area ratios of tumor cell apoptosis were larger in the r Ad/p53 + 5-FU group than that in the control, 5-FU and r Ad/p53 groups(P < 0.05), and were larger in the r Ad/p53 group than that of the control group(P < 0.05) and the 5-FU group at more than 48 h(P < 0.05). The p53 expression was higher in the r Ad/p53 and the r Ad/p53 + 5-FU groups than that of the control and 5-FU groups(P < 0.05), and were higher in the r Ad/p53 + 5-FU group than that of the r Ad/p53 group(P < 0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the r Ad/p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups(P < 0.05), and the expression of PKC was lower than that of the control, 5-FU and r Ad/p53 groups at more than 48 h(P < 0.05). In the r Ad/p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h(P < 0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h(P < 0.05).CONCLUSION5-FU combined with r Ad-p53 has a synergistic anticancer effect in SW480/5-FU(5-FU resistance), which contributes to reversal of 5-FU resistance. |
| doi_str_mv | 10.3748/wjg.v22.i32.7342 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4997648</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>90888889504849545150484954</cqvip_id><sourcerecordid>1819429358</sourcerecordid><originalsourceid>FETCH-LOGICAL-c398t-f4dd843719e7eaaea9e02493af9e7cded98eddcb751369de554dc2ea4e3be2613</originalsourceid><addsrcrecordid>eNpVUU1vGyEURFWrxvm491Rx7GVdPg1cKlVR01SKlEOaM8Lwdk20C86yduJbf3qx7Fgth8fTm3kziEHoEyVzroT--vLUzbeMzSNnc8UFe4dmjFHTMC3IezSjhKjGcKbO0HkpT4QwziX7iM6YWjAqNZmhPw-7BGMXyxQ9dqlWlzyMGNoW_IRzi-E1d5DypuCX2Idm2q0BryXHdQjY52EZE4SKTSssm5tHHBNebQaXKtbnWg96I5TqUQ3wlE-8bdzmS_ShdX2Bq-N9gR5vfvy-vm3u7n_-uv5-13hu9NS0IgQtuKIGFDgHzgBhwnDX1oEPEIyGEPxSScoXJoCUIngGTgBfAltQfoG-HXTXm-UAwUOaRtfb9RgHN-5sdtH-j6S4sl3eWmGMWghdBb4cBcb8vIEy2SEWD33vEtTfsVRTI5jhck8lB6ofcykjtCcbSuw-OFuDszU4W4Oz--Dqyud_n3daeEuqEvhRc5VT9xxTd-IYovfHSCK0MFJI-tbxv9lNp60</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1819429358</pqid></control><display><type>article</type><title>Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo</title><source>MEDLINE</source><source>Baishideng "World Journal of" online journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Xie, Qi ; Wu, Min-Yi ; Zhang, Ding-Xuan ; Yang, Yi-Ming ; Wang, Bao-Shuai ; Zhang, Jing ; Xu, Jin ; Zhong, Wei-De ; Hu, Jia-Ni</creator><creatorcontrib>Xie, Qi ; Wu, Min-Yi ; Zhang, Ding-Xuan ; Yang, Yi-Ming ; Wang, Bao-Shuai ; Zhang, Jing ; Xu, Jin ; Zhong, Wei-De ; Hu, Jia-Ni</creatorcontrib><description><![CDATA[AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53(r Ad-p53) combined with 5-fluorouracil(5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance.METHODS nude mice bearing human colon cancer SW480/5-FU(5-FU resistant) were randomly assigned to four groups(n = 25 each): control group, 5-FU group, r Ad-p53 group, and r Ad-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C(PKC), permeability-glycoprotein(P-gp) and multidrug resistance-associated protein 1(MRP1)(Western blot) and apoptosis(TUNEL) were determined.RESULTS The area ratios of tumor cell apoptosis were larger in the r Ad/p53 + 5-FU group than that in the control, 5-FU and r Ad/p53 groups(P < 0.05), and were larger in the r Ad/p53 group than that of the control group(P < 0.05) and the 5-FU group at more than 48 h(P < 0.05). The p53 expression was higher in the r Ad/p53 and the r Ad/p53 + 5-FU groups than that of the control and 5-FU groups(P < 0.05), and were higher in the r Ad/p53 + 5-FU group than that of the r Ad/p53 group(P < 0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the r Ad/p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups(P < 0.05), and the expression of PKC was lower than that of the control, 5-FU and r Ad/p53 groups at more than 48 h(P < 0.05). In the r Ad/p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h(P < 0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h(P < 0.05).CONCLUSION5-FU combined with r Ad-p53 has a synergistic anticancer effect in SW480/5-FU(5-FU resistance), which contributes to reversal of 5-FU resistance.]]></description><identifier>ISSN: 1007-9327</identifier><identifier>EISSN: 2219-2840</identifier><identifier>DOI: 10.3748/wjg.v22.i32.7342</identifier><identifier>PMID: 27621580</identifier><language>eng</language><publisher>United States: Baishideng Publishing Group Inc</publisher><subject>adenovirus-mediated ; Adenoviruses, Human - genetics ; Animals ; Antimetabolites, Antineoplastic - therapeutic use ; Basic Study ; cancer;Multidrug ; Cell Line, Tumor ; colon ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; Colonic Neoplasms - therapy ; Drug Resistance, Neoplasm - genetics ; Female ; Fluorouracil - therapeutic use ; Genes, p53 ; Genetic Therapy ; Human ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mutation ; nude ; p53;Xenografts ; resistance;5-Fluorouracil;Recombinant</subject><ispartof>World journal of gastroenterology : WJG, 2016-08, Vol.22 (32), p.7342-7352</ispartof><rights>The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-f4dd843719e7eaaea9e02493af9e7cded98eddcb751369de554dc2ea4e3be2613</citedby><cites>FETCH-LOGICAL-c398t-f4dd843719e7eaaea9e02493af9e7cded98eddcb751369de554dc2ea4e3be2613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/84123X/84123X.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997648/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997648/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27621580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xie, Qi</creatorcontrib><creatorcontrib>Wu, Min-Yi</creatorcontrib><creatorcontrib>Zhang, Ding-Xuan</creatorcontrib><creatorcontrib>Yang, Yi-Ming</creatorcontrib><creatorcontrib>Wang, Bao-Shuai</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Xu, Jin</creatorcontrib><creatorcontrib>Zhong, Wei-De</creatorcontrib><creatorcontrib>Hu, Jia-Ni</creatorcontrib><title>Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo</title><title>World journal of gastroenterology : WJG</title><addtitle>World Journal of Gastroenterology</addtitle><description><![CDATA[AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53(r Ad-p53) combined with 5-fluorouracil(5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance.METHODS nude mice bearing human colon cancer SW480/5-FU(5-FU resistant) were randomly assigned to four groups(n = 25 each): control group, 5-FU group, r Ad-p53 group, and r Ad-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C(PKC), permeability-glycoprotein(P-gp) and multidrug resistance-associated protein 1(MRP1)(Western blot) and apoptosis(TUNEL) were determined.RESULTS The area ratios of tumor cell apoptosis were larger in the r Ad/p53 + 5-FU group than that in the control, 5-FU and r Ad/p53 groups(P < 0.05), and were larger in the r Ad/p53 group than that of the control group(P < 0.05) and the 5-FU group at more than 48 h(P < 0.05). The p53 expression was higher in the r Ad/p53 and the r Ad/p53 + 5-FU groups than that of the control and 5-FU groups(P < 0.05), and were higher in the r Ad/p53 + 5-FU group than that of the r Ad/p53 group(P < 0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the r Ad/p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups(P < 0.05), and the expression of PKC was lower than that of the control, 5-FU and r Ad/p53 groups at more than 48 h(P < 0.05). In the r Ad/p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h(P < 0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h(P < 0.05).CONCLUSION5-FU combined with r Ad-p53 has a synergistic anticancer effect in SW480/5-FU(5-FU resistance), which contributes to reversal of 5-FU resistance.]]></description><subject>adenovirus-mediated</subject><subject>Adenoviruses, Human - genetics</subject><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>Basic Study</subject><subject>cancer;Multidrug</subject><subject>Cell Line, Tumor</subject><subject>colon</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colonic Neoplasms - therapy</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Fluorouracil - therapeutic use</subject><subject>Genes, p53</subject><subject>Genetic Therapy</subject><subject>Human</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Mutation</subject><subject>nude</subject><subject>p53;Xenografts</subject><subject>resistance;5-Fluorouracil;Recombinant</subject><issn>1007-9327</issn><issn>2219-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1vGyEURFWrxvm491Rx7GVdPg1cKlVR01SKlEOaM8Lwdk20C86yduJbf3qx7Fgth8fTm3kziEHoEyVzroT--vLUzbeMzSNnc8UFe4dmjFHTMC3IezSjhKjGcKbO0HkpT4QwziX7iM6YWjAqNZmhPw-7BGMXyxQ9dqlWlzyMGNoW_IRzi-E1d5DypuCX2Idm2q0BryXHdQjY52EZE4SKTSssm5tHHBNebQaXKtbnWg96I5TqUQ3wlE-8bdzmS_ShdX2Bq-N9gR5vfvy-vm3u7n_-uv5-13hu9NS0IgQtuKIGFDgHzgBhwnDX1oEPEIyGEPxSScoXJoCUIngGTgBfAltQfoG-HXTXm-UAwUOaRtfb9RgHN-5sdtH-j6S4sl3eWmGMWghdBb4cBcb8vIEy2SEWD33vEtTfsVRTI5jhck8lB6ofcykjtCcbSuw-OFuDszU4W4Oz--Dqyud_n3daeEuqEvhRc5VT9xxTd-IYovfHSCK0MFJI-tbxv9lNp60</recordid><startdate>20160828</startdate><enddate>20160828</enddate><creator>Xie, Qi</creator><creator>Wu, Min-Yi</creator><creator>Zhang, Ding-Xuan</creator><creator>Yang, Yi-Ming</creator><creator>Wang, Bao-Shuai</creator><creator>Zhang, Jing</creator><creator>Xu, Jin</creator><creator>Zhong, Wei-De</creator><creator>Hu, Jia-Ni</creator><general>Baishideng Publishing Group Inc</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>~WA</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><scope>5PM</scope></search><sort><creationdate>20160828</creationdate><title>Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo</title><author>Xie, Qi ; Wu, Min-Yi ; Zhang, Ding-Xuan ; Yang, Yi-Ming ; Wang, Bao-Shuai ; Zhang, Jing ; Xu, Jin ; Zhong, Wei-De ; Hu, Jia-Ni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-f4dd843719e7eaaea9e02493af9e7cded98eddcb751369de554dc2ea4e3be2613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>adenovirus-mediated</topic><topic>Adenoviruses, Human - genetics</topic><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - therapeutic use</topic><topic>Basic Study</topic><topic>cancer;Multidrug</topic><topic>Cell Line, Tumor</topic><topic>colon</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colonic Neoplasms - therapy</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Fluorouracil - therapeutic use</topic><topic>Genes, p53</topic><topic>Genetic Therapy</topic><topic>Human</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Mutation</topic><topic>nude</topic><topic>p53;Xenografts</topic><topic>resistance;5-Fluorouracil;Recombinant</topic><toplevel>online_resources</toplevel><creatorcontrib>Xie, Qi</creatorcontrib><creatorcontrib>Wu, Min-Yi</creatorcontrib><creatorcontrib>Zhang, Ding-Xuan</creatorcontrib><creatorcontrib>Yang, Yi-Ming</creatorcontrib><creatorcontrib>Wang, Bao-Shuai</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Xu, Jin</creatorcontrib><creatorcontrib>Zhong, Wei-De</creatorcontrib><creatorcontrib>Hu, Jia-Ni</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库- 镜像站点</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>World journal of gastroenterology : WJG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xie, Qi</au><au>Wu, Min-Yi</au><au>Zhang, Ding-Xuan</au><au>Yang, Yi-Ming</au><au>Wang, Bao-Shuai</au><au>Zhang, Jing</au><au>Xu, Jin</au><au>Zhong, Wei-De</au><au>Hu, Jia-Ni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo</atitle><jtitle>World journal of gastroenterology : WJG</jtitle><addtitle>World Journal of Gastroenterology</addtitle><date>2016-08-28</date><risdate>2016</risdate><volume>22</volume><issue>32</issue><spage>7342</spage><epage>7352</epage><pages>7342-7352</pages><issn>1007-9327</issn><eissn>2219-2840</eissn><abstract><![CDATA[AIM To investigate the anticancer effect of a recombinant adenovirus-mediated p53(r Ad-p53) combined with 5-fluorouracil(5-FU) in human colon cancer resistant to 5-FU in vivo and the mechanism of r Ad-p53 in reversal of 5-FU resistance.METHODS nude mice bearing human colon cancer SW480/5-FU(5-FU resistant) were randomly assigned to four groups(n = 25 each): control group, 5-FU group, r Ad-p53 group, and r Ad-p53 + 5-FU group. At 24 h, 48 h, 72 h, 120 h and 168 h after treatment, 5 mice were randomly selected from each group and sacrificed using an overdose of anesthetics. The tumors were removed and the protein expressions of p53, protein kinase C(PKC), permeability-glycoprotein(P-gp) and multidrug resistance-associated protein 1(MRP1)(Western blot) and apoptosis(TUNEL) were determined.RESULTS The area ratios of tumor cell apoptosis were larger in the r Ad/p53 + 5-FU group than that in the control, 5-FU and r Ad/p53 groups(P < 0.05), and were larger in the r Ad/p53 group than that of the control group(P < 0.05) and the 5-FU group at more than 48 h(P < 0.05). The p53 expression was higher in the r Ad/p53 and the r Ad/p53 + 5-FU groups than that of the control and 5-FU groups(P < 0.05), and were higher in the r Ad/p53 + 5-FU group than that of the r Ad/p53 group(P < 0.05). Overexpression of PKC, P-gp and MRP1 was observed in the 5-FU and control groups. In the r Ad/p53 + 5-FU group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups(P < 0.05), and the expression of PKC was lower than that of the control, 5-FU and r Ad/p53 groups at more than 48 h(P < 0.05). In the r Ad/p53 group, the expression of P-gp and MRP1 was lower that of the control and 5-FU groups at more than 48 h(P < 0.05), and the expression of PKC was lower than that of the control and 5-FU groups at more than 120 h(P < 0.05).CONCLUSION5-FU combined with r Ad-p53 has a synergistic anticancer effect in SW480/5-FU(5-FU resistance), which contributes to reversal of 5-FU resistance.]]></abstract><cop>United States</cop><pub>Baishideng Publishing Group Inc</pub><pmid>27621580</pmid><doi>10.3748/wjg.v22.i32.7342</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | adenovirus-mediated Adenoviruses, Human - genetics Animals Antimetabolites, Antineoplastic - therapeutic use Basic Study cancer Multidrug Cell Line, Tumor colon Colonic Neoplasms - genetics Colonic Neoplasms - pathology Colonic Neoplasms - therapy Drug Resistance, Neoplasm - genetics Female Fluorouracil - therapeutic use Genes, p53 Genetic Therapy Human Humans Male Mice Mice, Inbred BALB C Mice, Nude Mutation nude p53 Xenografts resistance 5-Fluorouracil Recombinant |
| title | Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo |
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