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.

Yue-qiang Chen;Hai-yan Song;Zhong-yan Zhou;Jiao Ma;Zhan-yang Luo;Ying Zhou;Jian-yi Wang;Sheng Liu;Xiang-hui Han

Institute of Chinese Traditional Surgery,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Institute of Digestive Diseases,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Shanghai TCM-integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China;Department of Liver Disease,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China

中国药理学报（英文版）

[1]Yue-qiang Chen;Hai-yan Song;Zhong-yan Zhou;Jiao Ma;Zhan-yang Luo;Ying Zhou;Jian-yi Wang;Sheng Liu;Xiang-hui Han-.Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGβ5 signaling)[J].中国药理学报（英文版）,2022(06):1544-1555

Osthole,Wenshen,Zhuanggu

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