Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice
Aim： To investigate the antitumor actions of the Crotalus durissus neurotoxin （crotoxin） on human esophageal carcinoma （Eca-109） cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. Methods： The growth-inhibitory effect was analyzed in Eca-109 cells using Ml-r assay. Cell morpholo...
Gespeichert in:
| Veröffentlicht in: | Acta pharmacologica Sinica 2013-02, Vol.34 (2), p.295-300 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 300 |
|---|---|
| container_issue | 2 |
| container_start_page | 295 |
| container_title | Acta pharmacologica Sinica |
| container_volume | 34 |
| creator | He, Jing-kang Wu, Xiang-sheng Wang, Yan Han, Rong Qin, Zheng-hong Xie, Yan |
| description | Aim： To investigate the antitumor actions of the Crotalus durissus neurotoxin （crotoxin） on human esophageal carcinoma （Eca-109） cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. Methods： The growth-inhibitory effect was analyzed in Eca-109 cells using Ml-r assay. Cell morphology changes in nuclei were observed using Hoechst 33342 staining, while apoptosis and cell cycle distribution were examined by flow cytometry. RT-PCR was used to measure the Bcl-2, p15, and caspase-3 p17 gene expression levels. A tumor transplantation model was established by inocu- lation of Eca-109 cells were into female Balb/c nude mice. Crotoxin （25, 50, and 100 mg/kg） was subcutaneously injected into the transplanted tumors every 2 d for a total of 10 injections. Tumor size and weight were measured. Bcl-2, p15, and caspase-3 p17 pro- tein expression in transplanted tumors was analyzed using Western blotting. Results.Crotoxin （25, 50, and 100 pg/mL） inhibited the growth of Eca-109 cells in a dose-dependent manner with inhibition rates of 22.9%, 35.8%, and 57.2%, respectively. Hoechst 33342 staining revealed apoptotic cells with pyknotic nuclear chromatin after crotoxin treatment. In Eca-109 cells, crotoxin induced apoptosis and G1 block, significantly upregulated the expression of p15 and caspase-3 p17 genes and downregulated the expression of Bcl-2 gene. Furthermore, crotoxin inhibited the growth of Eca-109 tumors in nude mice in a dose-dependent manner. Western blotting showed that crotoxin increased p15 and caspase-3 p17 protein levels and reduced Bcl-2 protein level in tumor specimens. Conclusion： Crotoxin inhibits the growth of Eca-109 cells in vitro via apoptosis induction and G1 block. Local administration of crotoxin inhibits the growth of subcutaneously transplanted Eca-109 cells in nude mice, possibly via increasing p15 and caspase-3 p17 protein expression and reducing Bcl-2 protein expression. |
| doi_str_mv | 10.1038/aps.2012.156 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4011616</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>44883816</cqvip_id><sourcerecordid>1562673231</sourcerecordid><originalsourceid>FETCH-LOGICAL-c509t-70faf9b10a362eab9d3e2274e326b0bc14743d66648dc82c1f3ae69b5daf7eff3</originalsourceid><addsrcrecordid>eNptkU1v1DAQhiMEoh9w44yMuHAgi7_iJBckVLUFqRIXOFsTZ7Jxldhb2yn0J_CvcbTLqiBOtjWP35l33qJ4xeiGUdF8gF3ccMr4hlXqSXHKalmVNa_k03xXNSslbcRJcRbjLaWCC9Y-L0644JQ3lJ4Wv66D_5FGYt1oO5t8eCA4DGhSJOB6MvsJzTJBIDOaEZyNcyR-ICb45H9aR1JASDO6lBUIRr8bYYswkUsDJaMtMThNe6kUwMXdBC5hfiyzD3H945YeyWwNviieDTBFfHk4z4vvV5ffLj6XN1-vv1x8uilNRdtU1nSAoe0YBaE4Qtf2AjmvJQquOtoZJmspeqWUbHrTcMMGAajaruphqLM1cV583Ovulm7G3uTZA0x6F-wM4UF7sPrvirOj3vp7LSljiqks8O4gEPzdgjHp2cbVJzj0S9Q5B67qddUZffsPeuuX4LI9zXiTk2k5l5l6v6fyVmMMOByHYVSvGeucsV4zXrUz_vqxgSP8J9QMlHsg5pLbYnjU9f-Cbw79R--2d_nLUVPKphFNNv0b0By_nA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1284089224</pqid></control><display><type>article</type><title>Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>He, Jing-kang ; Wu, Xiang-sheng ; Wang, Yan ; Han, Rong ; Qin, Zheng-hong ; Xie, Yan</creator><creatorcontrib>He, Jing-kang ; Wu, Xiang-sheng ; Wang, Yan ; Han, Rong ; Qin, Zheng-hong ; Xie, Yan</creatorcontrib><description>Aim： To investigate the antitumor actions of the Crotalus durissus neurotoxin （crotoxin） on human esophageal carcinoma （Eca-109） cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. Methods： The growth-inhibitory effect was analyzed in Eca-109 cells using Ml-r assay. Cell morphology changes in nuclei were observed using Hoechst 33342 staining, while apoptosis and cell cycle distribution were examined by flow cytometry. RT-PCR was used to measure the Bcl-2, p15, and caspase-3 p17 gene expression levels. A tumor transplantation model was established by inocu- lation of Eca-109 cells were into female Balb/c nude mice. Crotoxin （25, 50, and 100 mg/kg） was subcutaneously injected into the transplanted tumors every 2 d for a total of 10 injections. Tumor size and weight were measured. Bcl-2, p15, and caspase-3 p17 pro- tein expression in transplanted tumors was analyzed using Western blotting. Results.Crotoxin （25, 50, and 100 pg/mL） inhibited the growth of Eca-109 cells in a dose-dependent manner with inhibition rates of 22.9%, 35.8%, and 57.2%, respectively. Hoechst 33342 staining revealed apoptotic cells with pyknotic nuclear chromatin after crotoxin treatment. In Eca-109 cells, crotoxin induced apoptosis and G1 block, significantly upregulated the expression of p15 and caspase-3 p17 genes and downregulated the expression of Bcl-2 gene. Furthermore, crotoxin inhibited the growth of Eca-109 tumors in nude mice in a dose-dependent manner. Western blotting showed that crotoxin increased p15 and caspase-3 p17 protein levels and reduced Bcl-2 protein level in tumor specimens. Conclusion： Crotoxin inhibits the growth of Eca-109 cells in vitro via apoptosis induction and G1 block. Local administration of crotoxin inhibits the growth of subcutaneously transplanted Eca-109 cells in nude mice, possibly via increasing p15 and caspase-3 p17 protein expression and reducing Bcl-2 protein expression.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/aps.2012.156</identifier><identifier>PMID: 23202800</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Caspase 3 - genetics ; caspase-3 ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Crotalus - metabolism ; Crotalus durissus ; Crotoxin - pharmacology ; Crotoxin - therapeutic use ; Esophageal Neoplasms - drug therapy ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - pathology ; Esophagus - drug effects ; Esophagus - metabolism ; Esophagus - pathology ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Genes, bcl-2 - drug effects ; Humans ; Immunology ; Internal Medicine ; Medical Microbiology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Original ; original-article ; Pharmacology/Toxicology ; Vaccine ; 分子机制 ; 响尾蛇 ; 生长抑制作用 ; 神经毒素 ; 移植性 ; 裸鼠 ; 食管癌细胞</subject><ispartof>Acta pharmacologica Sinica, 2013-02, Vol.34 (2), p.295-300</ispartof><rights>CPS and SIMM 2013</rights><rights>Copyright Nature Publishing Group Feb 2013</rights><rights>Copyright © 2013 CPS and SIMM 2013 CPS and SIMM</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-70faf9b10a362eab9d3e2274e326b0bc14743d66648dc82c1f3ae69b5daf7eff3</citedby><cites>FETCH-LOGICAL-c509t-70faf9b10a362eab9d3e2274e326b0bc14743d66648dc82c1f3ae69b5daf7eff3</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/PMC4011616/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011616/$$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/23202800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Jing-kang</creatorcontrib><creatorcontrib>Wu, Xiang-sheng</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Han, Rong</creatorcontrib><creatorcontrib>Qin, Zheng-hong</creatorcontrib><creatorcontrib>Xie, Yan</creatorcontrib><title>Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim： To investigate the antitumor actions of the Crotalus durissus neurotoxin （crotoxin） on human esophageal carcinoma （Eca-109） cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. Methods： The growth-inhibitory effect was analyzed in Eca-109 cells using Ml-r assay. Cell morphology changes in nuclei were observed using Hoechst 33342 staining, while apoptosis and cell cycle distribution were examined by flow cytometry. RT-PCR was used to measure the Bcl-2, p15, and caspase-3 p17 gene expression levels. A tumor transplantation model was established by inocu- lation of Eca-109 cells were into female Balb/c nude mice. Crotoxin （25, 50, and 100 mg/kg） was subcutaneously injected into the transplanted tumors every 2 d for a total of 10 injections. Tumor size and weight were measured. Bcl-2, p15, and caspase-3 p17 pro- tein expression in transplanted tumors was analyzed using Western blotting. Results.Crotoxin （25, 50, and 100 pg/mL） inhibited the growth of Eca-109 cells in a dose-dependent manner with inhibition rates of 22.9%, 35.8%, and 57.2%, respectively. Hoechst 33342 staining revealed apoptotic cells with pyknotic nuclear chromatin after crotoxin treatment. In Eca-109 cells, crotoxin induced apoptosis and G1 block, significantly upregulated the expression of p15 and caspase-3 p17 genes and downregulated the expression of Bcl-2 gene. Furthermore, crotoxin inhibited the growth of Eca-109 tumors in nude mice in a dose-dependent manner. Western blotting showed that crotoxin increased p15 and caspase-3 p17 protein levels and reduced Bcl-2 protein level in tumor specimens. Conclusion： Crotoxin inhibits the growth of Eca-109 cells in vitro via apoptosis induction and G1 block. Local administration of crotoxin inhibits the growth of subcutaneously transplanted Eca-109 cells in nude mice, possibly via increasing p15 and caspase-3 p17 protein expression and reducing Bcl-2 protein expression.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Caspase 3 - genetics</subject><subject>caspase-3</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Crotalus - metabolism</subject><subject>Crotalus durissus</subject><subject>Crotoxin - pharmacology</subject><subject>Crotoxin - therapeutic use</subject><subject>Esophageal Neoplasms - drug therapy</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophagus - drug effects</subject><subject>Esophagus - metabolism</subject><subject>Esophagus - pathology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genes, bcl-2 - drug effects</subject><subject>Humans</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Original</subject><subject>original-article</subject><subject>Pharmacology/Toxicology</subject><subject>Vaccine</subject><subject>分子机制</subject><subject>响尾蛇</subject><subject>生长抑制作用</subject><subject>神经毒素</subject><subject>移植性</subject><subject>裸鼠</subject><subject>食管癌细胞</subject><issn>1671-4083</issn><issn>1745-7254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkU1v1DAQhiMEoh9w44yMuHAgi7_iJBckVLUFqRIXOFsTZ7Jxldhb2yn0J_CvcbTLqiBOtjWP35l33qJ4xeiGUdF8gF3ccMr4hlXqSXHKalmVNa_k03xXNSslbcRJcRbjLaWCC9Y-L0644JQ3lJ4Wv66D_5FGYt1oO5t8eCA4DGhSJOB6MvsJzTJBIDOaEZyNcyR-ICb45H9aR1JASDO6lBUIRr8bYYswkUsDJaMtMThNe6kUwMXdBC5hfiyzD3H945YeyWwNviieDTBFfHk4z4vvV5ffLj6XN1-vv1x8uilNRdtU1nSAoe0YBaE4Qtf2AjmvJQquOtoZJmspeqWUbHrTcMMGAajaruphqLM1cV583Ovulm7G3uTZA0x6F-wM4UF7sPrvirOj3vp7LSljiqks8O4gEPzdgjHp2cbVJzj0S9Q5B67qddUZffsPeuuX4LI9zXiTk2k5l5l6v6fyVmMMOByHYVSvGeucsV4zXrUz_vqxgSP8J9QMlHsg5pLbYnjU9f-Cbw79R--2d_nLUVPKphFNNv0b0By_nA</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>He, Jing-kang</creator><creator>Wu, Xiang-sheng</creator><creator>Wang, Yan</creator><creator>Han, Rong</creator><creator>Qin, Zheng-hong</creator><creator>Xie, Yan</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</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>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</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>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20130201</creationdate><title>Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice</title><author>He, Jing-kang ; Wu, Xiang-sheng ; Wang, Yan ; Han, Rong ; Qin, Zheng-hong ; Xie, Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-70faf9b10a362eab9d3e2274e326b0bc14743d66648dc82c1f3ae69b5daf7eff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Caspase 3 - genetics</topic><topic>caspase-3</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Crotalus - metabolism</topic><topic>Crotalus durissus</topic><topic>Crotoxin - pharmacology</topic><topic>Crotoxin - therapeutic use</topic><topic>Esophageal Neoplasms - drug therapy</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophagus - drug effects</topic><topic>Esophagus - metabolism</topic><topic>Esophagus - pathology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Genes, bcl-2 - drug effects</topic><topic>Humans</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Original</topic><topic>original-article</topic><topic>Pharmacology/Toxicology</topic><topic>Vaccine</topic><topic>分子机制</topic><topic>响尾蛇</topic><topic>生长抑制作用</topic><topic>神经毒素</topic><topic>移植性</topic><topic>裸鼠</topic><topic>食管癌细胞</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Jing-kang</creatorcontrib><creatorcontrib>Wu, Xiang-sheng</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Han, Rong</creatorcontrib><creatorcontrib>Qin, Zheng-hong</creatorcontrib><creatorcontrib>Xie, Yan</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-医药卫生</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>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Jing-kang</au><au>Wu, Xiang-sheng</au><au>Wang, Yan</au><au>Han, Rong</au><au>Qin, Zheng-hong</au><au>Xie, Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacologica Sinica</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>34</volume><issue>2</issue><spage>295</spage><epage>300</epage><pages>295-300</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Aim： To investigate the antitumor actions of the Crotalus durissus neurotoxin （crotoxin） on human esophageal carcinoma （Eca-109） cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. Methods： The growth-inhibitory effect was analyzed in Eca-109 cells using Ml-r assay. Cell morphology changes in nuclei were observed using Hoechst 33342 staining, while apoptosis and cell cycle distribution were examined by flow cytometry. RT-PCR was used to measure the Bcl-2, p15, and caspase-3 p17 gene expression levels. A tumor transplantation model was established by inocu- lation of Eca-109 cells were into female Balb/c nude mice. Crotoxin （25, 50, and 100 mg/kg） was subcutaneously injected into the transplanted tumors every 2 d for a total of 10 injections. Tumor size and weight were measured. Bcl-2, p15, and caspase-3 p17 pro- tein expression in transplanted tumors was analyzed using Western blotting. Results.Crotoxin （25, 50, and 100 pg/mL） inhibited the growth of Eca-109 cells in a dose-dependent manner with inhibition rates of 22.9%, 35.8%, and 57.2%, respectively. Hoechst 33342 staining revealed apoptotic cells with pyknotic nuclear chromatin after crotoxin treatment. In Eca-109 cells, crotoxin induced apoptosis and G1 block, significantly upregulated the expression of p15 and caspase-3 p17 genes and downregulated the expression of Bcl-2 gene. Furthermore, crotoxin inhibited the growth of Eca-109 tumors in nude mice in a dose-dependent manner. Western blotting showed that crotoxin increased p15 and caspase-3 p17 protein levels and reduced Bcl-2 protein level in tumor specimens. Conclusion： Crotoxin inhibits the growth of Eca-109 cells in vitro via apoptosis induction and G1 block. Local administration of crotoxin inhibits the growth of subcutaneously transplanted Eca-109 cells in nude mice, possibly via increasing p15 and caspase-3 p17 protein expression and reducing Bcl-2 protein expression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23202800</pmid><doi>10.1038/aps.2012.156</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1671-4083 |
| ispartof | Acta pharmacologica Sinica, 2013-02, Vol.34 (2), p.295-300 |
| issn | 1671-4083 1745-7254 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4011616 |
| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Biomedical and Life Sciences Biomedicine Caspase 3 - genetics caspase-3 Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Crotalus - metabolism Crotalus durissus Crotoxin - pharmacology Crotoxin - therapeutic use Esophageal Neoplasms - drug therapy Esophageal Neoplasms - genetics Esophageal Neoplasms - pathology Esophagus - drug effects Esophagus - metabolism Esophagus - pathology Female Gene Expression Regulation, Neoplastic - drug effects Genes, bcl-2 - drug effects Humans Immunology Internal Medicine Medical Microbiology Mice Mice, Inbred BALB C Mice, Nude Original original-article Pharmacology/Toxicology Vaccine 分子机制 响尾蛇 生长抑制作用 神经毒素 移植性 裸鼠 食管癌细胞 |
| title | Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T22%3A17%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Growth%20inhibitory%20effects%20and%20molecular%20mechanisms%20of%20crotoxin%20treatment%20in%20esophageal%20Eca-109%20cells%20and%20transplanted%20tumors%20in%20nude%20mice&rft.jtitle=Acta%20pharmacologica%20Sinica&rft.au=He,%20Jing-kang&rft.date=2013-02-01&rft.volume=34&rft.issue=2&rft.spage=295&rft.epage=300&rft.pages=295-300&rft.issn=1671-4083&rft.eissn=1745-7254&rft_id=info:doi/10.1038/aps.2012.156&rft_dat=%3Cproquest_pubme%3E1562673231%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1284089224&rft_id=info:pmid/23202800&rft_cqvip_id=44883816&rfr_iscdi=true |