@article{APS10588,
author = {Yue-qiang Chen and Hai-yan Song and Zhong-yan Zhou and Jiao Ma and Zhan-yang Luo and Ying Zhou and Jian-yi Wang and Sheng Liu and Xiang-hui Han},
title = {Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ ITGβ5 signaling},
journal = {Acta Pharmacologica Sinica},
volume = {43},
number = {6},
year = {2022},
keywords = {},
abstract = {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 integrin β5 (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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10588}
}