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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Norcantharidin anti-angiogenesis activity possibly through an endothelial cell pathway in human colorectal cancer
Tao Yu1, Fenggang Hou, Manman Liu
1Department of Oncology, Shanghai Chinese Medical Hospital, Shanghai, China. yutao1986cn@yahoo.com.cn
Abstract:
The present study was based on the unexpected discovery that norcantharidin exerted anti-angiogenesis activity when effects on growth of human colon cancer were studied. The aim was to further verify this finding and explore possible mechanisms using a tumor xenograft model in nude mice. We confirmed that norcantharidin (5 or 15 mg/kg) could inhibit angiogenesis of human colon cancer in vivo. In vitro, crossing river assay, cell adhesion assay and tube formation assay indicated that NCTD could reduce the migration, adhesion and vascular network tube formation ability of HUVECs. At the same time, the expression levels of VEGF and VEGFR-2 proteins which play important roles in angiogenesis were reduced as examined by western blotting analysis. Taken together, the results firstly showed NCTD could inhibit angiogenesis of human colon cancer in vivo, probably associated with effects on migration, adhesion and vascular network tube formation of HUVECs and expression levels of VEGF and VEGFR-2 proteins.
Insights
Norcantharidin (NCTD) effectively inhibits human colon cancer angiogenesis in vivo. This compound reduces cancer cell migration, adhesion, and tube formation by impacting VEGF and VEGFR-2 protein levels.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Angiogenesis is crucial for tumor growth and metastasis in human colon cancer.
- Norcantharidin (NCTD) was unexpectedly found to possess anti-angiogenic properties.
- Understanding NCTD's anti-angiogenic mechanisms is vital for developing new cancer therapies.
Purpose of the Study:
- To confirm and elucidate the anti-angiogenic effects of norcantharidin (NCTD) on human colon cancer.
- To investigate the underlying molecular mechanisms of NCTD's action in vitro and in vivo.
- To evaluate NCTD's efficacy in a human colon cancer xenograft model in nude mice.
Main Methods:
- In vivo studies using a human colon cancer xenograft model in nude mice.
- In vitro assays including crossing river, cell adhesion, and tube formation assays with HUVECs.
- Western blotting analysis to assess the expression levels of VEGF and VEGFR-2 proteins.
Main Results:
- Norcantharidin (5 or 15 mg/kg) significantly inhibited human colon cancer angiogenesis in vivo.
- NCTD reduced the migration, adhesion, and vascular network tube formation of HUVECs in vitro.
- Expression levels of VEGF and VEGFR-2 proteins were decreased by NCTD treatment.
Conclusions:
- Norcantharidin demonstrates significant in vivo anti-angiogenic activity against human colon cancer.
- NCTD's mechanism involves inhibiting HUVEC migration, adhesion, and tube formation.
- The anti-angiogenic effects of NCTD are likely associated with reduced VEGF and VEGFR-2 protein expression.
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