A novel four-step system for screening angiogenesis inhibitors

Area of Science:

• Oncology
• Pharmacology
• Biomedical Engineering

Background:

• Angiogenesis, the formation of new blood vessels, plays a crucial role in tumor growth and progression.
• Inhibiting angiogenesis is a promising strategy for cancer therapy, potentially offering advantages over existing treatments.
• Developing efficient screening systems for angiogenesis inhibitors is essential for advancing cancer drug discovery.

Purpose of the Study:

• To develop and validate a novel, multi-step system for screening angiogenesis inhibitors.
• To identify potential anti-cancer compounds by targeting angiogenesis.
• To confirm the efficacy of identified inhibitors in a preclinical cancer model.

Main Methods:

• A four-step screening approach was employed, starting with in vitro assays.
• Initial screening utilized the chorioallantoic membrane (CAM) assay, yolk sac membrane assay, and early chick embryo blood island assay.
• Final validation involved the MMTV-PyMT transgenic breast cancer mouse model for assessing anti-tumor effects.

Main Results:

• From an initial library of 480 compounds, four potent angiogenesis inhibitors were successfully isolated using the developed screening system.
• Treatment of the MMTV-PyMT mouse model with one of the identified inhibitors resulted in significant inhibition of tumor volume.
• The study confirmed the feasibility and effectiveness of the four-step screening system.

Conclusions:

• The developed four-step screening system is a feasible and effective method for identifying novel angiogenesis inhibitors.
• This system facilitates the discovery of potential anti-cancer agents targeting tumor angiogenesis.
• The identified inhibitors demonstrate significant potential for further development in cancer therapy.