Evaluation of morphology and angiogenesis of breast cancer in BALB/c mice using trypsin inhibitor from Cucumis melo seeds. In vitro and in vivo study

Introduction: Melon seeds, as an ex-cellent source of protease inhibitors, may have a protective role against tumor progression and angiogenesis. However, their effects on angiogenesis and the mechanism of their action against cancer progression remain elu-sive. This study aimed to investigate the effect of bioactive compounds of melon seed on the expression of angiogenesis genes in BALB/c mice with breast cancer.Material and methods: Trypsin in-hibitor (TI) was purified from the seed powder of Cucumis melo. Half -maximal inhibitory concentration was determined for TI, extract of melon seed powder (EXT), and tamoxifen (TAM) by the (3-(4,5-dimethylthi-azol-2-yl)-2,5-di phenyltetrazolium bromide (MTT) test. Also, breast tu-mor was induced by subcutaneous injection of MC4-L 2 cells in BALB/c inbred mice breast tissue. After tumor growth, mice were treated with TI, EXT, and TAM to examine their effects on the tumor characteristics and expres-sion of angiogenesis-related genes in-cluding MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) using the reverse transcription polymerase chain reaction method.Results: Trypsin inhibitor, EXT, TAM, and adjuvant treatment of TI + TAM resulted a reduction in expression of MMP-2, MMP-9, and VEGF. All treatments improved the breast tu-mor characteristics and the necrosis. The real-time polymerase chain re-action method verified the positive effects of the treatments on the breast cancer cell line and tumors.Conclusions: The results indicated that treatments with TI purified from Cucumis melo seeds and also combi-nation therapy of TI and TAM can be considered as an alternative therapy in breast cancer patients. Further studies are warranted.