Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGβ5 signaling  

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

机构地区：[1]Institute of Chinese Traditional Surgery,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China [2]Institute of Digestive Diseases,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China [3]Shanghai TCM-integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China [4]Department of Liver Disease,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China

出　　处：《Acta Pharmacologica Sinica》2022年第6期1544-1555,共12页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.81573973 and 81774308);the Natural Science Foundation of Shanghai(No.20ZR1458600);the Outstanding Traditional Chinese Medicine Academic Leader Program of Shanghai(No.ZY(2018-2020)-RCPY-1011).

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 integrinα3(ITGα3)and integrinβ5(ITGβ5)was upregulated in highly metastatic MDA-MB-231,MDA-MB-231BO 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.

关 键 词：OSTHOLE Wenshen Zhuanggu Formula breast cancer metastasis ITGα3 ITGβ5 FAK/Src/Rac1 pathway 

分 类 号：R737.9[医药卫生—肿瘤]