d Rhamnose β-hederin reverses chemoresistance of breast cancer cells by regulating exosome-mediated resistance transmission.

d Rhamnose β-hederin (DRβ-H), an active component extracted from the traditional Chinese medicinal plant Clematis ganpiniana, has been reported to be effective against breast cancer. Recent studies have also indicated that the isolated exosomes (D/exo) from docetaxel-resistant breast cancer cells MCF-7 (MCF-7/Doc) were associated with resistance transmission by delivering genetic cargo. However, the relevance of D/exo during DRβ-H exposure remains largely unclear. In the present work, exosomes were characterized by morphology and size distribution. We reinforced the significant role of D/exo in spreading chemoresistance from MCF-7/Doc to recipient sensitive cells after absorption and internalization. DRβ-H could reduce the formation and release of D/exo. Next, we demonstrated that DRβ-H was able to reverse docetaxel resistance and that D/exo was responsible for DRβ-H-mediated resistance reversal. We also found that DRβ-H could decrease the expressions of several most abundant miRNAs (miR-16, miR-23a, miR-24, miR-26a, and miR-27a) transported by D/exo. Target gene prediction and pathway analysis showed the involvement of these selected miRNAs in pathways related to treatment failure. Our results suggested that DRβ-H could reduce D/exo secretion from MCF-7/Doc cells and induce the reduction in resistance transmission via D/exo.