Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway
The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and a...
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| creator | Han, Sang Bae Hong, Jin Tae Lee, Dong Won Hwang, Jae Yeon Gu, Sun Mi Lee, Hye Lim Park, Ju Ho Ban, Jung Ok Hong, Ji Eun Son, Dong Ju Jung, Myung Hee |
| description | The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB. |
| doi_str_mv | 10.1155/2015/397563 |
| format | Article |
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Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2015/397563</identifier><identifier>PMID: 26491668</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Apoptosis ; Cancer cells ; Cancer therapies ; Cell growth ; Cell Line, Tumor ; Cellular signal transduction ; Cetuximab - pharmacology ; Chemotherapy ; Cisplatin ; Cisplatin - agonists ; Cisplatin - pharmacology ; Colon cancer ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - pathology ; Colorectal cancer ; Complications and side effects ; Cytotoxicity ; Deoxyribonucleic acid ; Development and progression ; DNA ; Drug interactions ; Drug Synergism ; Epidermal growth factor ; Genetic aspects ; Growth ; Health aspects ; Humans ; MAP Kinase Signaling System - drug effects ; Observations ; Radiation therapy ; Receptor, Epidermal Growth Factor - metabolism ; Rodents ; Tumors</subject><ispartof>BioMed research international, 2015-01, Vol.2015 (2015), p.1-13</ispartof><rights>Copyright © 2015 Dong Ju Son et al.</rights><rights>COPYRIGHT 2015 John Wiley & Sons, Inc.</rights><rights>Copyright © 2015 Dong Ju Son et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2015 Dong Ju Son et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-47e4348e977029ba052f102c9681c7e79a99561c5ac7b0833b9825a023212cce3</citedby><cites>FETCH-LOGICAL-c491t-47e4348e977029ba052f102c9681c7e79a99561c5ac7b0833b9825a023212cce3</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/PMC4600871/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600871/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26491668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Pešić, Milica</contributor><creatorcontrib>Han, Sang Bae</creatorcontrib><creatorcontrib>Hong, Jin Tae</creatorcontrib><creatorcontrib>Lee, Dong Won</creatorcontrib><creatorcontrib>Hwang, Jae Yeon</creatorcontrib><creatorcontrib>Gu, Sun Mi</creatorcontrib><creatorcontrib>Lee, Hye Lim</creatorcontrib><creatorcontrib>Park, Ju Ho</creatorcontrib><creatorcontrib>Ban, Jung Ok</creatorcontrib><creatorcontrib>Hong, Ji Eun</creatorcontrib><creatorcontrib>Son, Dong Ju</creatorcontrib><creatorcontrib>Jung, Myung Hee</creatorcontrib><title>Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.</description><subject>Apoptosis</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cellular signal transduction</subject><subject>Cetuximab - pharmacology</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Cisplatin - agonists</subject><subject>Cisplatin - pharmacology</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Complications and side effects</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>Drug interactions</subject><subject>Drug Synergism</subject><subject>Epidermal growth factor</subject><subject>Genetic aspects</subject><subject>Growth</subject><subject>Health aspects</subject><subject>Humans</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Observations</subject><subject>Radiation therapy</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Rodents</subject><subject>Tumors</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNks1uEzEUhUcIRKvSFXtkiQ0Chfrf4w1SNaRpRSVQC2vL43gyriZ2ansa8jI8Kw5pQ2FVb3wlfzq-99xTVa8R_IgQYycYInZCpGCcPKsOMUF0whFFz_c1IQfVcUo3sJwacSj5y-oAcyoR5_Vh9et6421cuJSdARe-d63LIW7AtOusyQmEDjQ2jz_dUrdA-zloXFoNOjsPggfn41J70ISh1I32xsZCDwOYxbDOPbhz-kHTFaJo5d6C6dWXyWe7sn5ufQbT2Rm4ssauyrfg2i28HpxfgG8692u9eVW96PSQ7PH9fVT9OJt-b84nl19nF83p5cSUQfKECksJra0UAmLZashwhyA2ktfICCuklpJxZJg2ooU1Ia2sMdMQE4ywMZYcVZ92uquxXdq5KZ1FPahVLHPHjQraqX9fvOvVItwpyoutAhWBd_cCMdyONmW1dMkUL7S3YUwKCSxkLSCCT0K5IFDQgr79D70JYywW_aFQ2TCl6C-10INVznehtGi2ouqUsrJ0hKUo1IcdZWJIKdpuPx2Capsltc2S2mWp0G8eG7JnH5JTgPc7oHd-rtfuaWq2ILbTj2DGCObkN_7H2PY</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Han, Sang Bae</creator><creator>Hong, Jin Tae</creator><creator>Lee, Dong Won</creator><creator>Hwang, Jae Yeon</creator><creator>Gu, Sun Mi</creator><creator>Lee, Hye Lim</creator><creator>Park, Ju Ho</creator><creator>Ban, Jung Ok</creator><creator>Hong, Ji Eun</creator><creator>Son, Dong Ju</creator><creator>Jung, Myung Hee</creator><general>Hindawi Publishing Corporation</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150101</creationdate><title>Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway</title><author>Han, Sang Bae ; Hong, Jin Tae ; Lee, Dong Won ; Hwang, Jae Yeon ; Gu, Sun Mi ; Lee, Hye Lim ; Park, Ju Ho ; Ban, Jung Ok ; Hong, Ji Eun ; Son, Dong Ju ; Jung, Myung Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-47e4348e977029ba052f102c9681c7e79a99561c5ac7b0833b9825a023212cce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Apoptosis</topic><topic>Cancer cells</topic><topic>Cancer therapies</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cellular signal transduction</topic><topic>Cetuximab - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Sang Bae</au><au>Hong, Jin Tae</au><au>Lee, Dong Won</au><au>Hwang, Jae Yeon</au><au>Gu, Sun Mi</au><au>Lee, Hye Lim</au><au>Park, Ju Ho</au><au>Ban, Jung Ok</au><au>Hong, Ji Eun</au><au>Son, Dong Ju</au><au>Jung, Myung Hee</au><au>Pešić, Milica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>2015</volume><issue>2015</issue><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>26491668</pmid><doi>10.1155/2015/397563</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Cancer cells Cancer therapies Cell growth Cell Line, Tumor Cellular signal transduction Cetuximab - pharmacology Chemotherapy Cisplatin Cisplatin - agonists Cisplatin - pharmacology Colon cancer Colonic Neoplasms - drug therapy Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Colorectal cancer Complications and side effects Cytotoxicity Deoxyribonucleic acid Development and progression DNA Drug interactions Drug Synergism Epidermal growth factor Genetic aspects Growth Health aspects Humans MAP Kinase Signaling System - drug effects Observations Radiation therapy Receptor, Epidermal Growth Factor - metabolism Rodents Tumors |
| title | Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway |
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