摘要Metastasis is the leading cause of death in breast cancer patients.Osthole,as an active compound detected in the traditional Chinese medicine Wenshen Zhuanggu Formula,has shown a promising anti-metastatic activity in human breast cancer cells,but the underlying mechanisms remain ambiguous.In this study we elucidated the anti-metastatic mechanisms of osthole in highly metastatic breast cancer cells and a zebrafish xenograft model.We showed that the expression of integrin α3(ITGα3)and integrinβ5(ITGβ5)was upregulated in highly metastatic MDA-MB-231,MDA-MB-231 BO breast cancer cell lines but was downregulated in poorly metastatic MCF-7 breast cancer cell line,which might be the key targets of osthole's anti-metastatic action.Furthermore,we showed that knockdown of ITGα3 and ITGβ5 attenuated breast cancer cell migration and invasion possibly via suppression of FAK/Src/Rac1 pathway,whereas overexpression of ITGα3 and ITGβ5 caused the opposite effects.Consistently,osthole significantly inhibited breast cancer metastasis by downregulating ITGα3/ITGβ5 signaling in vitro and in vivo.These results provide new evidence that osthole may be developed as a candidate therapeutic drug for metastatic breast cancer.