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Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography
- Source :
- BMC Cancer, Vol 11, Iss 1, p 28 (2011), BMC Cancer
- Publisher :
- Springer Nature
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....bcb7cb9c170c36a582b0a0c2689c1a7d
- Full Text :
- https://doi.org/10.1186/1471-2407-11-28