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Fluidic shear stress increases the anti-cancer effects of ROS-generating drugs in circulating tumor cells
Regmi S1; Fung TS2; Lim S1; Luo KQ2

PurposeMany anti-cancer drugs are used in chemotherapy; however, little is known about their efficacy against circulating tumor cells (CTCs). In this study, we investigated whether the pulsatile fluidic shear stress (SS) in human arteries can affect the efficacy of anti-cancer drugs.MethodsCancer cells were circulated in our microfluidic circulatory system, and their responses to drug and SS treatments were determined using various assays. Breast and cervical cancer cells that stably expressed apoptotic sensor proteins were used to determine apoptosis in real-time by fluorescence resonance energy transfer (FRET)-based imaging microscopy. The occurrence of cell death in non-sensor cells were revealed by annexin V and propidium iodide staining. Cell viability was determined by MTT assay. Intracellular reactive oxygen species (ROS) levels were determined by staining cells with two ROS-detecting dyes: 2,7-dichlorofluorescin diacetate and dihydroethidium.ResultsFluidic SS significantly increased the potency of the ROS-generating drugs doxorubicin (DOX) and cisplatin but had little effect on the non-ROS-generating drugs Taxol and etoposide. Co-treatment with SS and ROS-generating drugs dramatically elevated ROS levels in CTCs, while the addition of antioxidants abolished the pro-apoptotic effects of DOX and cisplatin. More importantly, the synergistic killing effects of SS and DOX or cisplatin were confirmed in circulated lung, breast, and cervical cancer cells, some of which have a strong metastatic ability.ConclusionsThese findings suggest that ROS-generating drugs are more potent than non-ROS-generating drugs for destroying CTCs under pulsatile fluidic conditions present in the bloodstream. This new information is highly valuable for developing novel therapies to eradicate CTCs in the circulation and prevent metastasis.

KeywordCirculating Tumor Cells Shear Stress Reactive Oxygen Species Apoptosis Anti-cancer Drugs Doxorubicin
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Indexed BySCI
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000447497300005
The Source to ArticleWOS
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.
2.Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
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GB/T 7714
Regmi S,Fung TS,Lim S,et al. Fluidic shear stress increases the anti-cancer effects of ROS-generating drugs in circulating tumor cells[J]. BREAST CANCER RESEARCH AND TREATMENT,2018,172(2):297-312.
APA Regmi S,Fung TS,Lim S,&Luo KQ.(2018).Fluidic shear stress increases the anti-cancer effects of ROS-generating drugs in circulating tumor cells.BREAST CANCER RESEARCH AND TREATMENT,172(2),297-312.
MLA Regmi S,et al."Fluidic shear stress increases the anti-cancer effects of ROS-generating drugs in circulating tumor cells".BREAST CANCER RESEARCH AND TREATMENT 172.2(2018):297-312.
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