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Evaluation of Angiogenesis Process after Metformin and LY294002 Treatment in Mammary Tumor
- Source :
- Anti-Cancer Agents in Medicinal Chemistry. 19:655-666
- Publication Year :
- 2019
- Publisher :
- Bentham Science Publishers Ltd., 2019.
-
Abstract
- Background:The angiogenesis process is regulated by many factors, such as Hypoxia-Inducible Factor-1 (HIF-1) and Vascular Endothelial Growth Factor (VEGF). Metformin has demonstrated its ability to inhibit cell growth and the LY294002 is the major inhibitor of PI3K/AKT/mTOR pathway that has antiangiogenic properties.Methods:Canine mammary tumor cell lines CMT-U229 and CF41 were treated with metformin and LY294002. Cell viability, protein and gene expression of VEGF and HIF-1 were determined in vitro. For the in vivo study, CF41 cells were inoculated in female athymic nude mice treated with either metformin or LY294002. The microvessel density by immunohistochemistry for CD31 as well as the gene and protein expression of HIF-1 and VEGF were evaluated.Results:The treatment with metformin and LY294002 was able to reduce the cellular viability after 24 hours. The protein and gene expression of HIF-1 and VEGF decreased after treatment with metformin and LY294002. In the in vivo study, there was a decrease in tumor size, protein and gene expression of HIF-1 and VEGFA, in addition to the decreasing of CD31 expression after all treatments.Conclusion:Our results demonstrate the effectiveness of metformin and LY294002 in controlling the angiogenesis process in mammary tumors by VEGF and HIF-1, the most important angiogenic markers.
- Subjects :
- Vascular Endothelial Growth Factor A
CD31
Cancer Research
Angiogenesis
Morpholines
Mice, Nude
Mammary Neoplasms, Animal
Mice
03 medical and health sciences
chemistry.chemical_compound
Dogs
0302 clinical medicine
Cell Line, Tumor
medicine
Animals
Dog Diseases
Viability assay
Protein kinase B
030304 developmental biology
Pharmacology
Mice, Inbred BALB C
0303 health sciences
Mammary tumor
Neovascularization, Pathologic
business.industry
Cobalt
Hypoxia-Inducible Factor 1, alpha Subunit
Metformin
Oxygen
Vascular endothelial growth factor
Vascular endothelial growth factor A
chemistry
Chromones
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 18715206
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Anti-Cancer Agents in Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....d80deb7177a6719e12d57afca65e58b0