Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography
| Autor: | Wei-Zhong Wu, Pei-li Fan, Hua-Xiang Xu, Ju-Bo Zhang, Yuquan Xiong, Peng-Yuan Zhuang, Zhao-You Tang, Hui-Chuan Sun, Ling-Qun Kong, Dong-Mei Gao, Hong Ding, Wei Zhang, Xiao-Dong Zhu, Lu Wang |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Male
Pathology medicine.medical_specialty Cancer Research Carcinoma Hepatocellular Indazoles Cell Survival Mice Nude Angiogenesis Inhibitors Apoptosis lcsh:RC254-282 Cell Line Pazopanib Mice Liver Neoplasms Experimental Surgical oncology Cell Line Tumor medicine Carcinoma Genetics Animals Humans Cells Cultured Cell Proliferation Ultrasonography Mice Inbred BALB C Sulfonamides Dose-Response Relationship Drug Cell growth business.industry Hep G2 Cells Image Enhancement lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Xenograft Model Antitumor Assays digestive system diseases Tumor Burden Pyrimidines Oncology Hepatocellular carcinoma Cancer research Blood Vessels Experimental pathology Stem cell business Research Article medicine.drug |
| Zdroj: | BMC Cancer, Vol 11, Iss 1, p 28 (2011) BMC Cancer |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-11-28 |
| Popis: | Background Antiangiogenesis is a promising therapy for advanced hepatocellular carcinoma (HCC), but the effects are difficult to be evaluated. Pazopanib (GW786034B) is a pan-vascular endothelial growth factor receptor inhibitor, the antitumor effects or antiangiogenic effects haven't been investigated in HCC. Methods In vitro direct effects of pazopanib on human HCC cell lines and endothelial cells were evaluated. In vivo antitumor effects were evaluated in three xenograft nude mice models. In the subcutaneous HCCLM3 model, intratumoral blood perfusion was detected by contrast-enhanced ultrasonography (CEUS), and serial quantitative parameters were profiled from the time-intensity curves of ultrasonograms. Results In vitro proliferation of various HCC cell lines were not inhibited by pazopanib. Pazopanib inhibited migration and invasion and induced apoptosis significantly in two HCC cell lines, HCCLM3 and PLC/PRF/5. Proliferation, migration, and tubule formation of human umbilical vein endothelial cells were inhibited by pazopanib in a dose-dependent manner. In vivo tumor growth was significantly inhibited by pazopanib in HCCLM3, HepG2, and PLC/PRF/5 xenograft models. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed. Mean transit time of the contrast media in hotspot areas of the tumors was reversely correlated with intratumoral microvessel density. Conclusions Antitumor effects of pazopanib in HCC xenografts may owe to its antiangiogenic effects, and the in vivo antiangiogenic effects could be evaluated by quantitative CEUS. |
| Databáze: | OpenAIRE |
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