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Published on: September 30, 2016
Effects of a novel immunomodulating agent, FTY720, on tumor growth and angiogenesis in hepatocellular carcinoma
Joanna W Y Ho1, Kwan Man, Chris K Sun
1Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Queen Mary Hospital, China.
Abstract:
In this study, we aimed to evaluate the potential anticancer and antiangiogenic effects of FTY720 on hepatocellular carcinoma. In vitro, chemosensitivity was tested on hepatoma cells, nontumorigenic, immortalized hepatocyte cells, as well as human umbilical vein endothelial cells (HUVEC). Moreover, effect of FTY720 on cell cycle and apoptosis was analyzed. In addition, a number of angiogenesis-associated assays were carried out. The in vivo effect of the drug on hepatocellular carcinoma tumor growth on nude mice was studied. Tissues obtained were analyzed in terms of proliferation, apoptosis, tumor microvessel density, and tumor vascular permeability. Compared with the MIHA cells, the hepatoma cell lines as well as HUVECs were found to be highly sensitive to the drugs in the aspect that FTY720 could induce G(1) arrest and apoptosis in the hepatoma cells. Furthermore, FTY720 significantly decreased invasion, migration, and capillary tube formation of HUVECs at very low doses. In vivo study showed that tumor growth was significantly suppressed in the FTY720-treated animals, and staining of the tissue sections showed decreased tumor cell proliferation and increased tumor cell apoptosis in the treatment groups. Interestingly, significant reductions in tumor microvessel density and tumor vascular permeability were also found in the FTY720-treated groups. In conclusion, FTY720 not only shows potent antiangiogenic effects but is also cytotoxic toward hepatoma cells. Results from our preclinical study suggest that FTY720 can be selected as a good candidate for the treatment of hepatocellular carcinoma.
Insights
FTY720 demonstrates significant anticancer and antiangiogenic properties against hepatocellular carcinoma. This drug induces apoptosis and G(1) arrest in cancer cells while inhibiting tumor growth and vascularization in vivo.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Hepatocellular carcinoma (HCC) is a significant global health concern with limited effective treatments.
- Angiogenesis plays a critical role in tumor growth and metastasis in HCC.
- Novel therapeutic strategies targeting both cancer cells and tumor vasculature are needed.
Purpose of the Study:
- To investigate the anticancer and antiangiogenic potential of FTY720 in hepatocellular carcinoma.
- To evaluate the in vitro and in vivo effects of FTY720 on HCC cells and tumor growth.
Main Methods:
- In vitro chemosensitivity assays on hepatoma cells and human umbilical vein endothelial cells (HUVECs).
- Analysis of cell cycle, apoptosis, invasion, migration, and capillary tube formation.
- In vivo studies in nude mice assessing tumor growth, proliferation, apoptosis, microvessel density, and vascular permeability.
Main Results:
- FTY720 induced G(1) arrest and apoptosis in hepatoma cells.
- FTY720 significantly inhibited HUVEC invasion, migration, and capillary tube formation.
- In vivo, FTY720 suppressed tumor growth, reduced proliferation, increased apoptosis, and decreased microvessel density and vascular permeability.
Conclusions:
- FTY720 exhibits potent cytotoxic effects against hepatoma cells.
- FTY720 demonstrates significant antiangiogenic activity by inhibiting endothelial cell function and tumor vascularization.
- FTY720 shows promise as a potential therapeutic agent for hepatocellular carcinoma.
