Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway
Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on co...
Gespeichert in:
| Veröffentlicht in: | International journal of oncology 2020-07, Vol.57 (1), p.183-196 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 196 |
|---|---|
| container_issue | 1 |
| container_start_page | 183 |
| container_title | International journal of oncology |
| container_volume | 57 |
| creator | Jiang, Fengqi Chen, Yaodong Ren, Shuo Li, Zizhuo Sun, Kan Xing, Yanwei Zhu, Yuekun Piao, Daxun |
| description | Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB‑D and further elucidate its molecular mechanism(s). DLD‑1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB‑D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB‑D‑treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB‑D in vivo. It was identified that CVB‑D inhibited the proliferation, migration, stemness, angiogenesis and epithelial‑mesenchymal transition of CRC cells, and induced apoptosis and S‑phase arrest. In addition, CVB‑D significantly inhibited the growth of xenografts. It is notable that CVB‑D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB‑D exerted anticancer effects through the CTHRC1‑AKT/ERK‑Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB‑D may offer a promising novel therapeutic approach for CRC treatment. |
| doi_str_mv | 10.3892/ijo.2020.5038 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7252468</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A628079229</galeid><sourcerecordid>A628079229</sourcerecordid><originalsourceid>FETCH-LOGICAL-c513t-8389a136a82f7b9be29519f0595557ac546a3aabceb4363af78ccd4b13e49fdc3</originalsourceid><addsrcrecordid>eNptks1u1DAUhSMEoqWwZIsiIbHL1D9xEm-QRmmhqJWQyrC2HI-T3JFjD7YzMDtegVfkSfCopXQk5IWvfL975HN1suw1RgvacHIOG7cgiKAFQ7R5kp3imuOClIQ-TTXCvKhKyk-yFyFsECKMIfw8O6GEYs44O82mdq-M24F33fwDrM4vcrAjdBBDrpxxXqsoTa6kVdrncZ6ch0FbHSDkO5B5HHXerq5uW_z756_l9er88vY6VV-sBJMHGKw0YId8K-P4Xe5fZs96aYJ-dX-fZV8_XK7aq-Lm88dP7fKmUAzTWDTJmcS0kg3p6453mnCGeY_SjxmrpWJlJamUndJdSSsq-7pRal12mOqS92tFz7L3d7rbuZv0WmkbvTRi62GSfi-cBHHcsTCKwe1ETRgpqyYJvL0X8O7brEMUGzf7ZCYIUmJKCcZV9Y8apNECbO-SmJogKLGsSINqTghP1OI_VDprPYFyVveQ3o8G3j0aGLU0cQzOzBGcDcdgcQcq70Lwun9wiJE4pEOkdIhDOsQhHYl_83gtD_TfONA_LEC3IQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2413321166</pqid></control><display><type>article</type><title>Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway</title><source>Spandidos Publications Journals</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Jiang, Fengqi ; Chen, Yaodong ; Ren, Shuo ; Li, Zizhuo ; Sun, Kan ; Xing, Yanwei ; Zhu, Yuekun ; Piao, Daxun</creator><creatorcontrib>Jiang, Fengqi ; Chen, Yaodong ; Ren, Shuo ; Li, Zizhuo ; Sun, Kan ; Xing, Yanwei ; Zhu, Yuekun ; Piao, Daxun</creatorcontrib><description>Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB‑D and further elucidate its molecular mechanism(s). DLD‑1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB‑D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB‑D‑treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB‑D in vivo. It was identified that CVB‑D inhibited the proliferation, migration, stemness, angiogenesis and epithelial‑mesenchymal transition of CRC cells, and induced apoptosis and S‑phase arrest. In addition, CVB‑D significantly inhibited the growth of xenografts. It is notable that CVB‑D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB‑D exerted anticancer effects through the CTHRC1‑AKT/ERK‑Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB‑D may offer a promising novel therapeutic approach for CRC treatment.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2020.5038</identifier><identifier>PMID: 32319595</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Adenocarcinoma - blood supply ; Adenocarcinoma - drug therapy ; Adenocarcinoma - pathology ; Animals ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis ; Autophagy ; Breast cancer ; Cancer treatment ; Carcinogenesis - drug effects ; Cell adhesion & migration ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Movement - genetics ; Cell Proliferation - drug effects ; Cell Proliferation - genetics ; Collagen ; Colonic Neoplasms - blood supply ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - pathology ; Colorectal cancer ; Drugs, Chinese Herbal - pharmacology ; Drugs, Chinese Herbal - therapeutic use ; Experiments ; Extracellular Matrix Proteins - antagonists & inhibitors ; Extracellular Matrix Proteins - genetics ; Extracellular Matrix Proteins - metabolism ; Female ; Gastric cancer ; Gene Knockdown Techniques ; Humans ; Instrument industry (Equipment) ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - genetics ; Metastasis ; Mice ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - pathology ; Polyclonal antibodies ; Proto-Oncogene Proteins c-akt - metabolism ; RNA ; RNA sequencing ; RNA, Small Interfering - metabolism ; RNA-Seq ; Scientific equipment industry ; Signal transduction ; Snail Family Transcription Factors - metabolism ; Stem cells ; Stomach cancer ; Tumorigenesis ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>International journal of oncology, 2020-07, Vol.57 (1), p.183-196</ispartof><rights>COPYRIGHT 2020 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2020</rights><rights>Copyright: © Jiang et al. 2020</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-8389a136a82f7b9be29519f0595557ac546a3aabceb4363af78ccd4b13e49fdc3</citedby><cites>FETCH-LOGICAL-c513t-8389a136a82f7b9be29519f0595557ac546a3aabceb4363af78ccd4b13e49fdc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32319595$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Fengqi</creatorcontrib><creatorcontrib>Chen, Yaodong</creatorcontrib><creatorcontrib>Ren, Shuo</creatorcontrib><creatorcontrib>Li, Zizhuo</creatorcontrib><creatorcontrib>Sun, Kan</creatorcontrib><creatorcontrib>Xing, Yanwei</creatorcontrib><creatorcontrib>Zhu, Yuekun</creatorcontrib><creatorcontrib>Piao, Daxun</creatorcontrib><title>Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB‑D and further elucidate its molecular mechanism(s). DLD‑1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB‑D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB‑D‑treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB‑D in vivo. It was identified that CVB‑D inhibited the proliferation, migration, stemness, angiogenesis and epithelial‑mesenchymal transition of CRC cells, and induced apoptosis and S‑phase arrest. In addition, CVB‑D significantly inhibited the growth of xenografts. It is notable that CVB‑D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB‑D exerted anticancer effects through the CTHRC1‑AKT/ERK‑Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB‑D may offer a promising novel therapeutic approach for CRC treatment.</description><subject>Adenocarcinoma - blood supply</subject><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - pathology</subject><subject>Animals</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Breast cancer</subject><subject>Cancer treatment</subject><subject>Carcinogenesis - drug effects</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - genetics</subject><subject>Collagen</subject><subject>Colonic Neoplasms - blood supply</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Drugs, Chinese Herbal - therapeutic use</subject><subject>Experiments</subject><subject>Extracellular Matrix Proteins - antagonists & inhibitors</subject><subject>Extracellular Matrix Proteins - genetics</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene Knockdown Techniques</subject><subject>Humans</subject><subject>Instrument industry (Equipment)</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - genetics</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Polyclonal antibodies</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>RNA, Small Interfering - metabolism</subject><subject>RNA-Seq</subject><subject>Scientific equipment industry</subject><subject>Signal transduction</subject><subject>Snail Family Transcription Factors - metabolism</subject><subject>Stem cells</subject><subject>Stomach cancer</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptks1u1DAUhSMEoqWwZIsiIbHL1D9xEm-QRmmhqJWQyrC2HI-T3JFjD7YzMDtegVfkSfCopXQk5IWvfL975HN1suw1RgvacHIOG7cgiKAFQ7R5kp3imuOClIQ-TTXCvKhKyk-yFyFsECKMIfw8O6GEYs44O82mdq-M24F33fwDrM4vcrAjdBBDrpxxXqsoTa6kVdrncZ6ch0FbHSDkO5B5HHXerq5uW_z756_l9er88vY6VV-sBJMHGKw0YId8K-P4Xe5fZs96aYJ-dX-fZV8_XK7aq-Lm88dP7fKmUAzTWDTJmcS0kg3p6453mnCGeY_SjxmrpWJlJamUndJdSSsq-7pRal12mOqS92tFz7L3d7rbuZv0WmkbvTRi62GSfi-cBHHcsTCKwe1ETRgpqyYJvL0X8O7brEMUGzf7ZCYIUmJKCcZV9Y8apNECbO-SmJogKLGsSINqTghP1OI_VDprPYFyVveQ3o8G3j0aGLU0cQzOzBGcDcdgcQcq70Lwun9wiJE4pEOkdIhDOsQhHYl_83gtD_TfONA_LEC3IQ</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Jiang, Fengqi</creator><creator>Chen, Yaodong</creator><creator>Ren, Shuo</creator><creator>Li, Zizhuo</creator><creator>Sun, Kan</creator><creator>Xing, Yanwei</creator><creator>Zhu, Yuekun</creator><creator>Piao, Daxun</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. Spandidos</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20200701</creationdate><title>Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway</title><author>Jiang, Fengqi ; Chen, Yaodong ; Ren, Shuo ; Li, Zizhuo ; Sun, Kan ; Xing, Yanwei ; Zhu, Yuekun ; Piao, Daxun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-8389a136a82f7b9be29519f0595557ac546a3aabceb4363af78ccd4b13e49fdc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenocarcinoma - blood supply</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - pathology</topic><topic>Animals</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Breast cancer</topic><topic>Cancer treatment</topic><topic>Carcinogenesis - drug effects</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Proliferation - genetics</topic><topic>Collagen</topic><topic>Colonic Neoplasms - blood supply</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Drugs, Chinese Herbal - therapeutic use</topic><topic>Experiments</topic><topic>Extracellular Matrix Proteins - antagonists & inhibitors</topic><topic>Extracellular Matrix Proteins - genetics</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene Knockdown Techniques</topic><topic>Humans</topic><topic>Instrument industry (Equipment)</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - genetics</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Polyclonal antibodies</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>RNA, Small Interfering - metabolism</topic><topic>RNA-Seq</topic><topic>Scientific equipment industry</topic><topic>Signal transduction</topic><topic>Snail Family Transcription Factors - metabolism</topic><topic>Stem cells</topic><topic>Stomach cancer</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Fengqi</creatorcontrib><creatorcontrib>Chen, Yaodong</creatorcontrib><creatorcontrib>Ren, Shuo</creatorcontrib><creatorcontrib>Li, Zizhuo</creatorcontrib><creatorcontrib>Sun, Kan</creatorcontrib><creatorcontrib>Xing, Yanwei</creatorcontrib><creatorcontrib>Zhu, Yuekun</creatorcontrib><creatorcontrib>Piao, Daxun</creatorcontrib><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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Fengqi</au><au>Chen, Yaodong</au><au>Ren, Shuo</au><au>Li, Zizhuo</au><au>Sun, Kan</au><au>Xing, Yanwei</au><au>Zhu, Yuekun</au><au>Piao, Daxun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>57</volume><issue>1</issue><spage>183</spage><epage>196</epage><pages>183-196</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><abstract>Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB‑D and further elucidate its molecular mechanism(s). DLD‑1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB‑D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB‑D‑treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB‑D in vivo. It was identified that CVB‑D inhibited the proliferation, migration, stemness, angiogenesis and epithelial‑mesenchymal transition of CRC cells, and induced apoptosis and S‑phase arrest. In addition, CVB‑D significantly inhibited the growth of xenografts. It is notable that CVB‑D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB‑D exerted anticancer effects through the CTHRC1‑AKT/ERK‑Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB‑D may offer a promising novel therapeutic approach for CRC treatment.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>32319595</pmid><doi>10.3892/ijo.2020.5038</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1019-6439 |
| ispartof | International journal of oncology, 2020-07, Vol.57 (1), p.183-196 |
| issn | 1019-6439 1791-2423 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7252468 |
| source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - blood supply Adenocarcinoma - drug therapy Adenocarcinoma - pathology Animals Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis Autophagy Breast cancer Cancer treatment Carcinogenesis - drug effects Cell adhesion & migration Cell cycle Cell growth Cell Line, Tumor Cell Movement - drug effects Cell Movement - genetics Cell Proliferation - drug effects Cell Proliferation - genetics Collagen Colonic Neoplasms - blood supply Colonic Neoplasms - drug therapy Colonic Neoplasms - pathology Colorectal cancer Drugs, Chinese Herbal - pharmacology Drugs, Chinese Herbal - therapeutic use Experiments Extracellular Matrix Proteins - antagonists & inhibitors Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism Female Gastric cancer Gene Knockdown Techniques Humans Instrument industry (Equipment) MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - genetics Metastasis Mice Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology Polyclonal antibodies Proto-Oncogene Proteins c-akt - metabolism RNA RNA sequencing RNA, Small Interfering - metabolism RNA-Seq Scientific equipment industry Signal transduction Snail Family Transcription Factors - metabolism Stem cells Stomach cancer Tumorigenesis Tumors Xenograft Model Antitumor Assays |
| title | Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T16%3A42%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cyclovirobuxine%20D%20inhibits%20colorectal%20cancer%20tumorigenesis%20via%20the%20CTHRC1%E2%80%91AKT/ERK%E2%80%91Snail%20signaling%20pathway&rft.jtitle=International%20journal%20of%20oncology&rft.au=Jiang,%20Fengqi&rft.date=2020-07-01&rft.volume=57&rft.issue=1&rft.spage=183&rft.epage=196&rft.pages=183-196&rft.issn=1019-6439&rft.eissn=1791-2423&rft_id=info:doi/10.3892/ijo.2020.5038&rft_dat=%3Cgale_pubme%3EA628079229%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2413321166&rft_id=info:pmid/32319595&rft_galeid=A628079229&rfr_iscdi=true |