Evaluation of Angiogenesis Process after Metformin and LY294002 Treatment in Mammary Tumor

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Angiogenesis, crucial for tumor growth, is regulated by factors including Hypoxia-Inducible Factor-1 (HIF-1) and Vascular Endothelial Growth Factor (VEGF).
• Metformin inhibits cell growth, while LY294002, a PI3K/AKT/mTOR pathway inhibitor, exhibits antiangiogenic properties.

Purpose of the Study:

• To investigate the antiangiogenic effects of metformin and LY294002 on canine mammary tumor cell lines.
• To evaluate the impact of these agents on VEGF and HIF-1 expression and tumor growth in vitro and in vivo.

Main Methods:

• Canine mammary tumor cell lines (CMT-U229, CF41) were treated with metformin and LY294002.
• In vitro: assessed cell viability and protein/gene expression of VEGF and HIF-1.
• In vivo: CF41 cells in nude mice were treated; tumor size, CD31, HIF-1, and VEGF expression were evaluated.

Main Results:

• Both metformin and LY294002 reduced canine mammary tumor cell viability and suppressed VEGF and HIF-1 expression.
• In vivo studies showed decreased tumor size, reduced CD31 expression (a marker of angiogenesis), and lower levels of HIF-1 and VEGF.

Conclusions:

• Metformin and LY294002 demonstrate efficacy in controlling angiogenesis in mammary tumors.
• These agents target key angiogenic markers, VEGF and HIF-1, highlighting their therapeutic potential.