Fluid Shear Stress Induces Drug Resistance to Doxorubicin and Paclitaxel in the Breast Cancer Cell Line MCF7

• Published in: Advanced therapeutics 2019-03, Vol.2 (3), p.n/a
• Main Authors: Triantafillu, Ursula Lea, Park, Seungjo, Kim, Yonghyun
• Format: Article
• Language: English
• Subjects: breast cancer; cancer stem cells; chemotherapy resistance; metastasis; shear stress
• ISSN: 2366-3987; 2366-3987
• DOI: 10.1002/adtp.201800112

Circulating tumor cells (CTCs) are known to have cancer stem cell (CSC) properties and survive physiological conditions of fluid shear stress (FSS). However, current chemotherapy screening techniques do not adequately recapitulate this FSS environment and are not predictive of a drug response. In this study, MCF7 and MDA‐MB‐231 cells under FSS are used as an in vitro model of CTCs. The effects of doxorubicin (DOX) and paclitaxel on sheared cells using WST8 assay and stemness (CD44+/CD24−) and apoptosis (Annexin V+/7‐AAD+) using flow cytometry are tested. Quantitative polymerase chain reaction is used to test gene expression. It is shown that suspension‐cultured and FSS treated MCF7 cells increase in drug resistance, especially with DOX. There is a synergistic increase in the CD44+/CD24− CSC‐like population and an increase in drug resistance‐related gene expression in MCF7 cells co‐treated with FSS and drugs. There is also a correlated increase in STAT3 and NANOG expression under FSS. To the best of the authors' knowledge, this is the first report to suggest that the increase in CSC‐like cells from FSS contributes to drug resistance via the STAT3/NANOG pathway. This increase in CTC drug resistance also highlights the importance of implementing FSS, which is unavailable in current drug screening techniques. Fluid shear stress plays an important role in the metastatic environment. The combination of fluid shear stress and chemotherapy increases the cancer stem cell population and CD44 expression. The combination of fluid shear stress and chemotherapy also increases drug resistance, with increased multidrug resistance protein 1 and breast cancer resistance protein expression via activation of the STAT3 transcription factor.