Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis
Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemi...
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| Veröffentlicht in: | Scientific reports 2016-10, Vol.6 (1), p.35788-35788, Article 35788 |
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| creator | Qi, Xiaofeng Xu, Wengguang Xie, Junqi Wang, Yufeng Han, Shengwei Wei, Zheng Ni, Yanhong Dong, Yingchun Han, Wei |
| description | Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both
in vitro
and
in vivo
, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers. |
| doi_str_mv | 10.1038/srep35788 |
| format | Article |
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in vitro
and
in vivo
, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep35788</identifier><identifier>PMID: 27762347</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/31 ; 14 ; 38 ; 38/77 ; 631/67/1665 ; 631/67/327 ; 96 ; Animals ; Antineoplastic Agents - pharmacology ; Carcinoma, Squamous Cell - drug therapy ; Cell Line, Tumor ; Cisplatin - pharmacology ; Disease Models, Animal ; Gene Expression Regulation - drug effects ; Heterografts ; Humanities and Social Sciences ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors ; Metformin - pharmacology ; Mice, Nude ; multidisciplinary ; Neoplasm Transplantation ; NF-kappa B - antagonists & inhibitors ; Science ; Treatment Outcome</subject><ispartof>Scientific reports, 2016-10, Vol.6 (1), p.35788-35788, Article 35788</ispartof><rights>The Author(s) 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-c807c7432f84c1c00ee5b38ea504944cabde20ba6464a3ddd85c956e5ee48e523</citedby><cites>FETCH-LOGICAL-c410t-c807c7432f84c1c00ee5b38ea504944cabde20ba6464a3ddd85c956e5ee48e523</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/PMC5071902/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5071902/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27762347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qi, Xiaofeng</creatorcontrib><creatorcontrib>Xu, Wengguang</creatorcontrib><creatorcontrib>Xie, Junqi</creatorcontrib><creatorcontrib>Wang, Yufeng</creatorcontrib><creatorcontrib>Han, Shengwei</creatorcontrib><creatorcontrib>Wei, Zheng</creatorcontrib><creatorcontrib>Ni, Yanhong</creatorcontrib><creatorcontrib>Dong, Yingchun</creatorcontrib><creatorcontrib>Han, Wei</creatorcontrib><title>Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both
in vitro
and
in vivo
, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers.</description><subject>13</subject><subject>13/31</subject><subject>14</subject><subject>38</subject><subject>38/77</subject><subject>631/67/1665</subject><subject>631/67/327</subject><subject>96</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Cell Line, Tumor</subject><subject>Cisplatin - pharmacology</subject><subject>Disease Models, Animal</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Heterografts</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors</subject><subject>Metformin - pharmacology</subject><subject>Mice, Nude</subject><subject>multidisciplinary</subject><subject>Neoplasm Transplantation</subject><subject>NF-kappa B - antagonists & inhibitors</subject><subject>Science</subject><subject>Treatment Outcome</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><recordid>eNptkc9u1DAQhyMEolXpgRdAPkKltI7_bJwLElQsrVTgAmfLcSa7rhI79Tio8AY8Dlceos-Eo21XRcIXW5pPn2fmVxQvK3paUa7OMMLEZa3Uk-KQUSFLxhl7-uh9UBwjXtN8JGtE1TwvDlhdrxgX9WHx6xOkPsTReYLg0SX3E5CkLZAIOAWPQEJPQjQDwZvZjGFGYmEYiDXROh9GQ1Ig1uE0mJQlKYJJI_iUHTHMmy1xfuva7A1-MX1el3d_3p9dXK7L6u43QbfxWW1uHb4onvVmQDi-v4-Kb-sPX88vyqsvHy_P312VVlQ0lVbR2taCs14JW1lKAWTLFRhJRSOENW0HjLZmJVbC8K7rlLSNXIEEEAok40fF2513mtsROpt7zdPpKbrRxB86GKf_rXi31ZvwXUtaVw1dBK_vBTHczIBJjw6XnRgPeT26UlxKqrha0Dc71MaAOah-_01F9ZKe3qeX2VeP-9qTD1ll4GQHYC75DUR9HeaY14f_sf0FGImo8w</recordid><startdate>20161020</startdate><enddate>20161020</enddate><creator>Qi, Xiaofeng</creator><creator>Xu, Wengguang</creator><creator>Xie, Junqi</creator><creator>Wang, Yufeng</creator><creator>Han, Shengwei</creator><creator>Wei, Zheng</creator><creator>Ni, Yanhong</creator><creator>Dong, Yingchun</creator><creator>Han, Wei</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161020</creationdate><title>Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis</title><author>Qi, Xiaofeng ; Xu, Wengguang ; Xie, Junqi ; Wang, Yufeng ; Han, Shengwei ; Wei, Zheng ; Ni, Yanhong ; Dong, Yingchun ; Han, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-c807c7432f84c1c00ee5b38ea504944cabde20ba6464a3ddd85c956e5ee48e523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13</topic><topic>13/31</topic><topic>14</topic><topic>38</topic><topic>38/77</topic><topic>631/67/1665</topic><topic>631/67/327</topic><topic>96</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Cell Line, Tumor</topic><topic>Cisplatin - pharmacology</topic><topic>Disease Models, Animal</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Heterografts</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors</topic><topic>Metformin - pharmacology</topic><topic>Mice, Nude</topic><topic>multidisciplinary</topic><topic>Neoplasm Transplantation</topic><topic>NF-kappa B - antagonists & inhibitors</topic><topic>Science</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Xiaofeng</creatorcontrib><creatorcontrib>Xu, Wengguang</creatorcontrib><creatorcontrib>Xie, Junqi</creatorcontrib><creatorcontrib>Wang, Yufeng</creatorcontrib><creatorcontrib>Han, Shengwei</creatorcontrib><creatorcontrib>Wei, Zheng</creatorcontrib><creatorcontrib>Ni, Yanhong</creatorcontrib><creatorcontrib>Dong, Yingchun</creatorcontrib><creatorcontrib>Han, Wei</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>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>Qi, Xiaofeng</au><au>Xu, Wengguang</au><au>Xie, Junqi</au><au>Wang, Yufeng</au><au>Han, Shengwei</au><au>Wei, Zheng</au><au>Ni, Yanhong</au><au>Dong, Yingchun</au><au>Han, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-10-20</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>35788</spage><epage>35788</epage><pages>35788-35788</pages><artnum>35788</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both
in vitro
and
in vivo
, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27762347</pmid><doi>10.1038/srep35788</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/31 14 38 38/77 631/67/1665 631/67/327 96 Animals Antineoplastic Agents - pharmacology Carcinoma, Squamous Cell - drug therapy Cell Line, Tumor Cisplatin - pharmacology Disease Models, Animal Gene Expression Regulation - drug effects Heterografts Humanities and Social Sciences Humans Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors Metformin - pharmacology Mice, Nude multidisciplinary Neoplasm Transplantation NF-kappa B - antagonists & inhibitors Science Treatment Outcome |
| title | Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis |
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