Effects of metformin on CD133+ colorectal cancer cells in diabetic patients
In diabetic patients complicated with colorectal cancer (CRC), metformin treatment was reported to have diverse correlation with CRC-specific mortality. In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs) in breast and pancreatic cancers and glioblastoma....
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| Veröffentlicht in: | PloS one 2013-11, Vol.8 (11), p.e81264 |
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| description | In diabetic patients complicated with colorectal cancer (CRC), metformin treatment was reported to have diverse correlation with CRC-specific mortality. In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs) in breast and pancreatic cancers and glioblastoma. Although cscs play a critical role in the resistance to 5-fluorouracil (5-FU) chemotherapy in CRC patients, the effect of metformin on cscs in CRC patients and the synergistic effect of metformin in combination with 5-FU on cscs are not reported. In the present study pathological examinations were performed in 86 CRC patients complicated with type 2 DM who had been divided into a metformin group and a non-metformin group. Comparisons regarding pathological type, incidence of metastasis, expression of CD133 and β-catenin were conducted between the two groups. We explored the synergistic effects of metformin in combination with 5-FU on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of SW620 human colorectal cancer cell lines. The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells. These findings provide an important complement to previous study. Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes. |
| doi_str_mv | 10.1371/journal.pone.0081264 |
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In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs) in breast and pancreatic cancers and glioblastoma. Although cscs play a critical role in the resistance to 5-fluorouracil (5-FU) chemotherapy in CRC patients, the effect of metformin on cscs in CRC patients and the synergistic effect of metformin in combination with 5-FU on cscs are not reported. In the present study pathological examinations were performed in 86 CRC patients complicated with type 2 DM who had been divided into a metformin group and a non-metformin group. Comparisons regarding pathological type, incidence of metastasis, expression of CD133 and β-catenin were conducted between the two groups. We explored the synergistic effects of metformin in combination with 5-FU on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of SW620 human colorectal cancer cell lines. The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells. These findings provide an important complement to previous study. Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081264</identifier><identifier>PMID: 24278407</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>5-Fluorouracil ; AC133 Antigen ; Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Antidiabetics ; Antigens, CD - metabolism ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; beta Catenin - metabolism ; Breast cancer ; Cancer ; Cancer metastasis ; Cancer research ; Cancer therapies ; Cell cycle ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell survival ; Chemotherapy ; Cholesterol ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - complications ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Correlation ; Demographics ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes therapy ; Diabetics ; Endocrinology ; Female ; Fluorouracil - pharmacology ; Glioblastoma ; Glycoproteins - metabolism ; Health aspects ; Health risk assessment ; Humans ; Hypoglycemic Agents - pharmacology ; Hypoglycemic Agents - therapeutic use ; Immunohistochemistry ; Kinases ; Laboratories ; Lipoproteins ; Male ; Medical prognosis ; Medical records ; Metabolism ; Metastases ; Metastasis ; Metformin ; Metformin - pharmacology ; Metformin - therapeutic use ; Middle Aged ; Mortality ; Pancreas ; Pancreatic cancer ; Patients ; Peptides - metabolism ; Proteins ; Stem cells ; Synergistic effect ; Synergistic effects ; Systematic review ; Tumor cell lines ; Type 2 diabetes ; β-Catenin</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e81264</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Zhang et al 2013 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6505d3ebba9e210ae722aed33b9bcdd503522e227e5b2538d57ccb7e766256bd3</citedby><cites>FETCH-LOGICAL-c692t-6505d3ebba9e210ae722aed33b9bcdd503522e227e5b2538d57ccb7e766256bd3</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/PMC3836781/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836781/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24278407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Liu, Chunming</contributor><creatorcontrib>Zhang, Yanfei</creatorcontrib><creatorcontrib>Guan, Meiping</creatorcontrib><creatorcontrib>Zheng, Zongji</creatorcontrib><creatorcontrib>Zhang, Qian</creatorcontrib><creatorcontrib>Gao, Fang</creatorcontrib><creatorcontrib>Xue, Yaoming</creatorcontrib><title>Effects of metformin on CD133+ colorectal cancer cells in diabetic patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In diabetic patients complicated with colorectal cancer (CRC), metformin treatment was reported to have diverse correlation with CRC-specific mortality. In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs) in breast and pancreatic cancers and glioblastoma. Although cscs play a critical role in the resistance to 5-fluorouracil (5-FU) chemotherapy in CRC patients, the effect of metformin on cscs in CRC patients and the synergistic effect of metformin in combination with 5-FU on cscs are not reported. In the present study pathological examinations were performed in 86 CRC patients complicated with type 2 DM who had been divided into a metformin group and a non-metformin group. Comparisons regarding pathological type, incidence of metastasis, expression of CD133 and β-catenin were conducted between the two groups. We explored the synergistic effects of metformin in combination with 5-FU on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of SW620 human colorectal cancer cell lines. The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells. These findings provide an important complement to previous study. Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes.</description><subject>5-Fluorouracil</subject><subject>AC133 Antigen</subject><subject>Adenocarcinoma</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antidiabetics</subject><subject>Antigens, CD - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>beta Catenin - metabolism</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer metastasis</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell survival</subject><subject>Chemotherapy</subject><subject>Cholesterol</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - complications</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Correlation</subject><subject>Demographics</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes therapy</subject><subject>Diabetics</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Fluorouracil - pharmacology</subject><subject>Glioblastoma</subject><subject>Glycoproteins - metabolism</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Immunohistochemistry</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Lipoproteins</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical records</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Metformin</subject><subject>Metformin - pharmacology</subject><subject>Metformin - therapeutic use</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Patients</subject><subject>Peptides - metabolism</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>Synergistic effect</subject><subject>Synergistic effects</subject><subject>Systematic review</subject><subject>Tumor cell lines</subject><subject>Type 2 diabetes</subject><subject>β-Catenin</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7rr6DUQLgiAyY5qkSfsiLOOqgwsL_nsNSXozkyFtZpNU9NubdbrLFBQkDwk3v3tycjlF8bRCy4rw6s3Oj2GQbrn3AywRairM6L3itGoJXjCMyP2j80nxKMYdQjVpGHtYnGCKeUMRPy0-XRgDOsXSm7KHZHzo7VD6oVy9qwh5XWrvfMiAdKWWg4ZQanAulhnqrFSQrC73MlkYUnxcPDDSRXgy7WfFt_cXX1cfF5dXH9ar88uFZi1OC1ajuiOglGwBV0gCx1hCR4hqle66GpEaY8CYQ61wdtzVXGvFgTOGa6Y6clY8P-junY9imkMUFWWoRrQlJBPrA9F5uRP7YHsZfgkvrfhT8GEjZMjWHYiGM0o4R0YboMxwVZO2bTkoZoimILPW2-m1UfXQ6fzTIN1MdH4z2K3Y-B-CNITxpsoCLyaB4K9HiOkflidqI7MrOxifxXRvoxbnNMtwjCjK1PIvVF4d9FbnJBib67OGV7OGzCT4mTZyjFGsv3z-f_bq-5x9ecRuQbq0jd6NyfohzkF6AHXwMQYwd5OrkLgJ8u00xE2QxRTk3PbseOp3TbfJJb8BnybsWQ</recordid><startdate>20131121</startdate><enddate>20131121</enddate><creator>Zhang, Yanfei</creator><creator>Guan, Meiping</creator><creator>Zheng, Zongji</creator><creator>Zhang, Qian</creator><creator>Gao, Fang</creator><creator>Xue, Yaoming</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131121</creationdate><title>Effects of metformin on CD133+ colorectal cancer cells in diabetic patients</title><author>Zhang, Yanfei ; Guan, Meiping ; Zheng, Zongji ; Zhang, Qian ; Gao, Fang ; Xue, Yaoming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6505d3ebba9e210ae722aed33b9bcdd503522e227e5b2538d57ccb7e766256bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>5-Fluorouracil</topic><topic>AC133 Antigen</topic><topic>Adenocarcinoma</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antidiabetics</topic><topic>Antigens, CD - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>beta Catenin - metabolism</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer metastasis</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell survival</topic><topic>Chemotherapy</topic><topic>Cholesterol</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - complications</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Correlation</topic><topic>Demographics</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes therapy</topic><topic>Diabetics</topic><topic>Endocrinology</topic><topic>Female</topic><topic>Fluorouracil - 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In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs) in breast and pancreatic cancers and glioblastoma. Although cscs play a critical role in the resistance to 5-fluorouracil (5-FU) chemotherapy in CRC patients, the effect of metformin on cscs in CRC patients and the synergistic effect of metformin in combination with 5-FU on cscs are not reported. In the present study pathological examinations were performed in 86 CRC patients complicated with type 2 DM who had been divided into a metformin group and a non-metformin group. Comparisons regarding pathological type, incidence of metastasis, expression of CD133 and β-catenin were conducted between the two groups. We explored the synergistic effects of metformin in combination with 5-FU on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of SW620 human colorectal cancer cell lines. The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells. These findings provide an important complement to previous study. Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24278407</pmid><doi>10.1371/journal.pone.0081264</doi><tpages>e81264</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2013-11, Vol.8 (11), p.e81264 |
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| recordid | cdi_plos_journals_1460504933 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 5-Fluorouracil AC133 Antigen Adenocarcinoma Adult Aged Aged, 80 and over Antidiabetics Antigens, CD - metabolism Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects beta Catenin - metabolism Breast cancer Cancer Cancer metastasis Cancer research Cancer therapies Cell cycle Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cell survival Chemotherapy Cholesterol Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - complications Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Correlation Demographics Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes therapy Diabetics Endocrinology Female Fluorouracil - pharmacology Glioblastoma Glycoproteins - metabolism Health aspects Health risk assessment Humans Hypoglycemic Agents - pharmacology Hypoglycemic Agents - therapeutic use Immunohistochemistry Kinases Laboratories Lipoproteins Male Medical prognosis Medical records Metabolism Metastases Metastasis Metformin Metformin - pharmacology Metformin - therapeutic use Middle Aged Mortality Pancreas Pancreatic cancer Patients Peptides - metabolism Proteins Stem cells Synergistic effect Synergistic effects Systematic review Tumor cell lines Type 2 diabetes β-Catenin |
| title | Effects of metformin on CD133+ colorectal cancer cells in diabetic patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T23%3A05%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20metformin%20on%20CD133+%20colorectal%20cancer%20cells%20in%20diabetic%20patients&rft.jtitle=PloS%20one&rft.au=Zhang,%20Yanfei&rft.date=2013-11-21&rft.volume=8&rft.issue=11&rft.spage=e81264&rft.pages=e81264-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0081264&rft_dat=%3Cgale_plos_%3EA478172040%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1460504933&rft_id=info:pmid/24278407&rft_galeid=A478172040&rft_doaj_id=oai_doaj_org_article_87643770fcfe46f7b539997eb6f3c4ea&rfr_iscdi=true |