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Background: Angiogenesis provides the oxygen and nutrients needed for metastasis and tumor growth, so by inhibiting angiogenesis, metastasis to other parts of the body can be prevented at the first steps of cancer. 5-Fluorouracil (5-FU) as a common chemotherapy drug and Quercetin as a natural compound both have anti-angiogenic properties. Objectives: In the current study improvement of the anti-angiogenic property of 5-FU by combination with quercetin was investigated. Methods: After treating the cells with alone or a combination of drugs the angiogenesis, vascular endothelial growth factor receptors (VEGFRs) gene expression, migration, and viability of the cells were evaluated using chicken chorioallantoic membrane (CAM) assay, real-time RT-PCR, wound healing and MTT assay, respectively. Results: Treatment with alone 5-FU and Que led to a significant reduction in angiogenesis, VEGFR2 and VEGFR1gene expression, migration, and Cell viability. The reductions were significant in the combination state compared to alone treatment. Conclusions: The results showed that the combination treatment with Que with 5-FU enhances the anti-angiogenic property of 5-FU, so it can be proposed as a potential anti-angiogenic and as a result anti-metastatic treatment for future animal studies. [ABSTRACT FROM AUTHOR]

Objective(s): Breast cancer (BC) cells' ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) facilitate cancer cell migration. 5-fluorouracil is a frequently applied chemotherapeutic agent in cancer treatment with destructive side effects on normal tissues. Hence, researchers have focused on finding a way to reduce the dose of chemotherapeutic drugs. Quercetin, a natural polyphenolic compound, has inhibitory effects on proliferation and migration of tumor cells. This study evaluated the effect of the combination of Quercetin and 5-fluorouracil on migration of the MDA-MB-231 breast cancer cell line. Materials and Methods: The effect of Quercetin, 5-fluorouracil, and their combination on MDA-MB-231 breast cancer cell proliferation was investigated through MTT assay. Inhibition of tumor cell migration was examined by wound healing assay. Finally, the effect of treatments on gene expression of MMP-2 and MMP-9 was evaluated by quantitative real-time PCR. Results: The IC50 values for Quercetin and 5-fluorouracil after 48 hr treatment were 295 µM and 525 µM, respectively. The combination index (CI) for Quercetin and 5-fluorouracil was <1, indicating synergy between them. The combination of Quercetin plus 5-fluorouracil resulted in a significant reduction in migration rate and MMP-2 and MMP-9 gene expressions of MDA-MB-231 cancer cells compared with the individual application of 5-FU. Conclusion: Quercetin enhances the suppressory effect of 5-fluorouracil on migration of BC cells. The combination of Quercetin and 5-fluorouracil can be an attractive field for future studies. [ABSTRACT FROM AUTHOR]