Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis
<p>Abstract</p> <p>Background</p> <p>Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor β. Dovitinib is currently in clinical tria...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-12-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://www.translational-medicine.com/content/10/1/245 |
| _version_ | 1818230840050581504 |
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| author | Chen Zhi-Yuan Shi Ming Peng Li-Xia Wei Wei Li Xin-Jian Guo Zhi-Xing Li Shu-Hong Zhong Chong Qian Chao-Nan Guo Rong-Ping |
| author_facet | Chen Zhi-Yuan Shi Ming Peng Li-Xia Wei Wei Li Xin-Jian Guo Zhi-Xing Li Shu-Hong Zhong Chong Qian Chao-Nan Guo Rong-Ping |
| author_sort | Chen Zhi-Yuan |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor β. Dovitinib is currently in clinical trials for the treatment of hepatocellular carcinoma (HCC).</p> <p>Method</p> <p>In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib.</p> <p>Results</p> <p>Tumor growth and pulmonary metastasis were significantly suppressed in an orthotopic HCC model. Immunoblotting revealed that among known dovitinib targets, only PDGFR-β was expressed in two HCC cell lines, while four of five endothelial lines expressed PDGFR-β, FGFR-1, and VEGFR-2. Dovitinib inhibited endothelial cell proliferation and motility at 0.04 μmol/L, a pharmacologically relevant concentration; it was unable to inhibit the proliferation or motility of HCC cells at the same concentration. Immunohistochemical analyses showed that dovitinib significantly decreased the microvessel density of xenograft tumors, inhibiting proliferation and inducing apoptosis in HCC cells.</p> <p>Conclusion</p> <p>Our findings indicate that dovitinib inhibits HCC growth and metastasis preferentially through an antiangiogenic mechanism, not through direct targeting of HCC cells.</p> |
| first_indexed | 2024-12-12T10:40:53Z |
| format | Article |
| id | doaj.art-bb1b7969bac84e00a928351ab950e85d |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-12T10:40:53Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-bb1b7969bac84e00a928351ab950e85d2022-12-22T00:27:03ZengBMCJournal of Translational Medicine1479-58762012-12-0110124510.1186/1479-5876-10-245Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasisChen Zhi-YuanShi MingPeng Li-XiaWei WeiLi Xin-JianGuo Zhi-XingLi Shu-HongZhong ChongQian Chao-NanGuo Rong-Ping<p>Abstract</p> <p>Background</p> <p>Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor β. Dovitinib is currently in clinical trials for the treatment of hepatocellular carcinoma (HCC).</p> <p>Method</p> <p>In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib.</p> <p>Results</p> <p>Tumor growth and pulmonary metastasis were significantly suppressed in an orthotopic HCC model. Immunoblotting revealed that among known dovitinib targets, only PDGFR-β was expressed in two HCC cell lines, while four of five endothelial lines expressed PDGFR-β, FGFR-1, and VEGFR-2. Dovitinib inhibited endothelial cell proliferation and motility at 0.04 μmol/L, a pharmacologically relevant concentration; it was unable to inhibit the proliferation or motility of HCC cells at the same concentration. Immunohistochemical analyses showed that dovitinib significantly decreased the microvessel density of xenograft tumors, inhibiting proliferation and inducing apoptosis in HCC cells.</p> <p>Conclusion</p> <p>Our findings indicate that dovitinib inhibits HCC growth and metastasis preferentially through an antiangiogenic mechanism, not through direct targeting of HCC cells.</p>http://www.translational-medicine.com/content/10/1/245DovitinibEndothelial cellsHepatocellular carcinomaTumor growthTumor metastasis |
| spellingShingle | Chen Zhi-Yuan Shi Ming Peng Li-Xia Wei Wei Li Xin-Jian Guo Zhi-Xing Li Shu-Hong Zhong Chong Qian Chao-Nan Guo Rong-Ping Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis Journal of Translational Medicine Dovitinib Endothelial cells Hepatocellular carcinoma Tumor growth Tumor metastasis |
| title | Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis |
| title_full | Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis |
| title_fullStr | Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis |
| title_full_unstemmed | Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis |
| title_short | Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis |
| title_sort | dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis |
| topic | Dovitinib Endothelial cells Hepatocellular carcinoma Tumor growth Tumor metastasis |
| url | http://www.translational-medicine.com/content/10/1/245 |
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