anti-angiogenic and anti-metastatic effectsof hesperidin in Xenograft model of breast cancer

Background: Breast cancer is most common malignancy andhas high and mortality rates also Breast Cancer treatment hasbeen shown ineffectiveness and challenging due to the presenceof drug resistance and many other side effects . Hesperidin isflavonoids from citrus species, have been extensively evaluatedfor their anti-cancer potentials. This study examined the antiangiogenicand anti-metastatic effects of hesperidin On humanbreast cancer animal model.Materials and Methods: Cell viability assay was performanceusing MTT. Eliza assay was applied to determined serum levelof INFɣ and IL-۴. ۴T۱-induced mammary tumours in BALB/cfemale mice were used as an in vivo model to study the effectof hesperidin on the occurrence of metastasis and angiogenesis.Real-time PCR (CD۱۰۵, VEGFa, VEGFR۲ and COX۲ as angiogenesismarkers ) were conducted to assess the effect of hesperidintreatment on mRNA expression. Protein expression ofMMP۲, MMP۹ and VEGF gene related to metastasis in animalmodel of breast cancer was investigated by immunohistochemistry(IHC) .P≤۰.۰۵ considered statistically significant.Results: The number of ۴T۱ cells in the ۷۲-hour group is higherthan the other two groups. Also, the observed difference incell survival at ۲۴-hour, ۴۸-hour and ۷۲-hour times was statisticallysignificant (P=۰. Also, the decrease in the number of stemcells in the ۷۲-hour time compared to other times was statisticallysignificant (P=۰.۰۰۳۲). Statistical analysis showed that anincrease of INFɣ levels and decrease of IL-۴ were significant(P≤۰.۰۵) in hesperidin treated groups. Moreover, hesperidin decreaseangiogenesis markers significantly (P≤۰.۰۵).Conclusion: The results of this study suggest that hesperidincan be used as a potential treatment with or without standardtherapy (doxorubicin) in future clinical trials.