Abstract 1622: Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis
| العنوان: | Abstract 1622: Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis |
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| المؤلفون: | Rong Ping Guo, Wei Wei, Li-Xia Peng, Chao-Nan Qian, Shu-Hong Li, Zhi Yuan Chen, Ming Shi, Xinjian Li, Chong Zhong, Zhixing Guo |
| المصدر: | Cancer Research. 73:1622-1622 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Cancer Research, Pathology, medicine.medical_specialty, biology, business.industry, Cancer, medicine.disease, Receptor tyrosine kinase, Metastasis, Vascular endothelial growth factor, chemistry.chemical_compound, Oncology, Growth factor receptor, chemistry, Fibroblast growth factor receptor, Cancer cell, biology.protein, Cancer research, Medicine, business, Platelet-derived growth factor receptor |
| الوصف: | Background: 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), however, its cellular target is not clarified. Method: In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib. Results: 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 0.05 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. Conclusion: Our findings indicate that dovitinib inhibits HCC growth and metastasis preferentially through an antiangiogenic mechanism, not through direct targeting of HCC cells. Citation Format: Zhi-Yuan Chen, Ming Shi, Li-Xia Peng, Wei Wei, Xin-Jian Li, Zhi-Xing Guo, Shu-Hong Li, Chong Zhong, Chao-Nan Qian, Rong-Ping Guo. Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1622. doi:10.1158/1538-7445.AM2013-1622 |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::da776e708ee20d17ba61855a73506513Test https://doi.org/10.1158/1538-7445.am2013-1622Test |
| رقم الانضمام: | edsair.doi...........da776e708ee20d17ba61855a73506513 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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