Ultrasound reverses chemoresistance in breast cancer stem cell like cells by altering ABCG2 expression.

Abstract:

:Doxorubicin (DOX) resistance in breast cancer largely results from the breast cancer stem cell like cells (BCSCs) which could be targetted to improve the efficacy of chemotherapy. Cell permeabilization using microbubbles (MBs) and ultrasound (US) have the potential for delivering molecules into the cytoplasm. We aim to evaluate a new methodology of US on BCSCs. First, our findings indicated that ALDHA1+ spheres which were derived from fresh primary breast cancer samples displayed stem cell like features and were resistant to DOX. In patient cohort, we revealed the presence of a variable fraction of ALDHA1+cells in nine out of ten. We, for the first time, showed a new US-MB treatment condition which could be used on ALDHA1+ BCSCs by fluorescence measurement and calcein assay. Next, we demonstrated the efficacy of combined treatment on human BCSCs in vitro and in vivo using DOX and US-MB: the combined treatment with much reduced drug dosage significantly suppressed the stem cell like features of BCSCs and induced BCSCs apoptosis. Furthermore, we suggested that decreased ABCG2 level might be one of the mechanisms by which US-MB medicated DOX treatment. In conclusion, this new US-MB treatment condition has clinical potential in breast cancer therapy by targetting BCSCs; thereby holding benefits for breast cancer patients.

journal_name

Biosci Rep

journal_title

Bioscience reports

authors

Guo L,Zheng P,Fan H,Wang H,Xu W,Zhou W

doi

10.1042/BSR20171137

subject

Has Abstract

pub_date

2017-11-09 00:00:00

issue

6

eissn

0144-8463

issn

1573-4935

pii

BSR20171137

journal_volume

37

pub_type

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