The anti-tumor properties of two tumstatin peptide fragments in human gastric carcinoma
Aim： The aim was to study the anti-tumor activities and mechanisms of two synthetic peptide fragments of tumstatin （alpha3 （iV） NCl domain） in human gastric carcinoma cells in vitro and in vivo. Methods： MTr assay and cell cycle assay were used to study the anti-tumor and anti-angiogenic activities...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2009-09, Vol.30 (9), p.1307-1315 |
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| creator | Li, Ying-jie Sun, Li-chun He, Yan Liu, Xing-han Liu, Miao Wang, Qi-min Jin, Xiao-ming |
| description | Aim： The aim was to study the anti-tumor activities and mechanisms of two synthetic peptide fragments of tumstatin （alpha3 （iV） NCl domain） in human gastric carcinoma cells in vitro and in vivo. Methods： MTr assay and cell cycle assay were used to study the anti-tumor and anti-angiogenic activities of two peptide fragments in vitro. Apoptosis induced by the two peptide fragments was demonstrated by TUNEL assay and morphological observation. The orthotopic tumor model was established to investigate the activities of two peptide fragments in vivo. Intratumor vascularization and the expressions of VEGF, bFGF, Fas, FasL, Bax, Bcl-2, and caspase 3 were determined using immunohistochemistry and Western blot analysis. Results： Peptide 19 inhibited SGC-7901 proliferation and induced apoptosis both in vitro and in vivo. Notably, peptide 21 suppressed the proliferation of HUVEC-12 cells in vitro. Each peptide arrested both cell lines at the G0/G1 phase of the cell cycle, and they also synergistically suppressed in vitro and in vivo tumor growth. Immunohistochemistry and Western blot analysis revealed the strong expression of Fas, FasL and caspase 3 in orthotopic tumor tissues treated with peptide 19 alone or in combination with peptide 21. Decreased expressions of VEGF and bFGF and decreased microvessel density （MVD） in orthotopic tumor tissues were seen in mice treated with peptide 21 alone or in combination with peptide 19. Conclusion： Two tumstatin peptide fragments facilitate two unique antitumor activities. Thus, they are drug candidates in the treatment of gastric carcinoma. |
| doi_str_mv | 10.1038/aps.2009.111 |
| format | Article |
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Methods： MTr assay and cell cycle assay were used to study the anti-tumor and anti-angiogenic activities of two peptide fragments in vitro. Apoptosis induced by the two peptide fragments was demonstrated by TUNEL assay and morphological observation. The orthotopic tumor model was established to investigate the activities of two peptide fragments in vivo. Intratumor vascularization and the expressions of VEGF, bFGF, Fas, FasL, Bax, Bcl-2, and caspase 3 were determined using immunohistochemistry and Western blot analysis. Results： Peptide 19 inhibited SGC-7901 proliferation and induced apoptosis both in vitro and in vivo. Notably, peptide 21 suppressed the proliferation of HUVEC-12 cells in vitro. Each peptide arrested both cell lines at the G0/G1 phase of the cell cycle, and they also synergistically suppressed in vitro and in vivo tumor growth. Immunohistochemistry and Western blot analysis revealed the strong expression of Fas, FasL and caspase 3 in orthotopic tumor tissues treated with peptide 19 alone or in combination with peptide 21. Decreased expressions of VEGF and bFGF and decreased microvessel density （MVD） in orthotopic tumor tissues were seen in mice treated with peptide 21 alone or in combination with peptide 19. Conclusion： Two tumstatin peptide fragments facilitate two unique antitumor activities. Thus, they are drug candidates in the treatment of gastric carcinoma.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/aps.2009.111</identifier><identifier>PMID: 19701238</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Autoantigens - pharmacology ; Biomedical and Life Sciences ; Biomedicine ; Cell Division - drug effects ; Cell Line, Tumor ; Collagen Type IV - pharmacology ; Female ; Immunology ; Internal Medicine ; Medical Microbiology ; Mice ; Mice, Inbred BALB C ; Neovascularization, Pathologic - drug therapy ; Original ; original-article ; Peptide Fragments - pharmacology ; Pharmacology/Toxicology ; Stomach Neoplasms - drug therapy ; Vaccine ; Xenograft Model Antitumor Assays ; 肽片段</subject><ispartof>Acta pharmacologica Sinica, 2009-09, Vol.30 (9), p.1307-1315</ispartof><rights>CPS and SIMM 2009</rights><rights>Copyright Nature Publishing Group Sep 2009</rights><rights>Copyright © 2009 CPS and SIMM 2009 CPS and SIMM</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-21ab4e7bae3e687c510769ae52058dda0dcd6f07ff56074d7344d541ede2b12d3</citedby><cites>FETCH-LOGICAL-c475t-21ab4e7bae3e687c510769ae52058dda0dcd6f07ff56074d7344d541ede2b12d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/95561A/95561A.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007175/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007175/$$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/19701238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ying-jie</creatorcontrib><creatorcontrib>Sun, Li-chun</creatorcontrib><creatorcontrib>He, Yan</creatorcontrib><creatorcontrib>Liu, Xing-han</creatorcontrib><creatorcontrib>Liu, Miao</creatorcontrib><creatorcontrib>Wang, Qi-min</creatorcontrib><creatorcontrib>Jin, Xiao-ming</creatorcontrib><title>The anti-tumor properties of two tumstatin peptide fragments in human gastric carcinoma</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim： The aim was to study the anti-tumor activities and mechanisms of two synthetic peptide fragments of tumstatin （alpha3 （iV） NCl domain） in human gastric carcinoma cells in vitro and in vivo. Methods： MTr assay and cell cycle assay were used to study the anti-tumor and anti-angiogenic activities of two peptide fragments in vitro. Apoptosis induced by the two peptide fragments was demonstrated by TUNEL assay and morphological observation. The orthotopic tumor model was established to investigate the activities of two peptide fragments in vivo. Intratumor vascularization and the expressions of VEGF, bFGF, Fas, FasL, Bax, Bcl-2, and caspase 3 were determined using immunohistochemistry and Western blot analysis. Results： Peptide 19 inhibited SGC-7901 proliferation and induced apoptosis both in vitro and in vivo. Notably, peptide 21 suppressed the proliferation of HUVEC-12 cells in vitro. Each peptide arrested both cell lines at the G0/G1 phase of the cell cycle, and they also synergistically suppressed in vitro and in vivo tumor growth. Immunohistochemistry and Western blot analysis revealed the strong expression of Fas, FasL and caspase 3 in orthotopic tumor tissues treated with peptide 19 alone or in combination with peptide 21. Decreased expressions of VEGF and bFGF and decreased microvessel density （MVD） in orthotopic tumor tissues were seen in mice treated with peptide 21 alone or in combination with peptide 19. Conclusion： Two tumstatin peptide fragments facilitate two unique antitumor activities. Thus, they are drug candidates in the treatment of gastric carcinoma.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Autoantigens - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Division - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Collagen Type IV - pharmacology</subject><subject>Female</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Original</subject><subject>original-article</subject><subject>Peptide Fragments - pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Vaccine</subject><subject>Xenograft Model Antitumor 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C</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Original</topic><topic>original-article</topic><topic>Peptide Fragments - pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Vaccine</topic><topic>Xenograft Model Antitumor Assays</topic><topic>肽片段</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ying-jie</creatorcontrib><creatorcontrib>Sun, Li-chun</creatorcontrib><creatorcontrib>He, Yan</creatorcontrib><creatorcontrib>Liu, Xing-han</creatorcontrib><creatorcontrib>Liu, Miao</creatorcontrib><creatorcontrib>Wang, Qi-min</creatorcontrib><creatorcontrib>Jin, Xiao-ming</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-自然科学</collection><collection>中文科技期刊数据库-自然科学-生物科学</collection><collection>中文科技期刊数据库- 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Xiao-ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The anti-tumor properties of two tumstatin peptide fragments in human gastric carcinoma</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacologica Sinica</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>30</volume><issue>9</issue><spage>1307</spage><epage>1315</epage><pages>1307-1315</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Aim： The aim was to study the anti-tumor activities and mechanisms of two synthetic peptide fragments of tumstatin （alpha3 （iV） NCl domain） in human gastric carcinoma cells in vitro and in vivo. Methods： MTr assay and cell cycle assay were used to study the anti-tumor and anti-angiogenic activities of two peptide fragments in vitro. Apoptosis induced by the two peptide fragments was demonstrated by TUNEL assay and morphological observation. The orthotopic tumor model was established to investigate the activities of two peptide fragments in vivo. Intratumor vascularization and the expressions of VEGF, bFGF, Fas, FasL, Bax, Bcl-2, and caspase 3 were determined using immunohistochemistry and Western blot analysis. Results： Peptide 19 inhibited SGC-7901 proliferation and induced apoptosis both in vitro and in vivo. Notably, peptide 21 suppressed the proliferation of HUVEC-12 cells in vitro. Each peptide arrested both cell lines at the G0/G1 phase of the cell cycle, and they also synergistically suppressed in vitro and in vivo tumor growth. Immunohistochemistry and Western blot analysis revealed the strong expression of Fas, FasL and caspase 3 in orthotopic tumor tissues treated with peptide 19 alone or in combination with peptide 21. Decreased expressions of VEGF and bFGF and decreased microvessel density （MVD） in orthotopic tumor tissues were seen in mice treated with peptide 21 alone or in combination with peptide 19. Conclusion： Two tumstatin peptide fragments facilitate two unique antitumor activities. Thus, they are drug candidates in the treatment of gastric carcinoma.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19701238</pmid><doi>10.1038/aps.2009.111</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic Agents - pharmacology Apoptosis - drug effects Autoantigens - pharmacology Biomedical and Life Sciences Biomedicine Cell Division - drug effects Cell Line, Tumor Collagen Type IV - pharmacology Female Immunology Internal Medicine Medical Microbiology Mice Mice, Inbred BALB C Neovascularization, Pathologic - drug therapy Original original-article Peptide Fragments - pharmacology Pharmacology/Toxicology Stomach Neoplasms - drug therapy Vaccine Xenograft Model Antitumor Assays 肽片段 |
| title | The anti-tumor properties of two tumstatin peptide fragments in human gastric carcinoma |
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